RAPID COMMUNICATION
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
Abstract |
|---|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Fas antigen is a cell surface protein that mediates apoptosis, and it is expressed in various cells and tissues.
Fas ligand binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells. Malfunction of the Fas-
Fas ligand system causes lymphoproliferative disorders and autoimmune diseases, whereas its exacerbation may cause tissue destruction. We hypothesize that excessive apoptosis mediated by Fas-Fas ligand interaction may damage alveolar epithelial cells and result in pulmonary fibrosis. Mice were allowed to inhale repeatedly an aerosolized anti-Fas antibody for 14 days. The nuclei of bronchial and alveolar epithelial
cells were positively stained by in situ DNA nick end labeling. Electron microscopy demonstrated apoptotic changes in bronchial and alveolar epithelial cells. Histologic findings and hydroxyproline content
showed the development of pulmonary fibrosis, which was dependent on the dose of anti-Fas antibody.
The repeated inhalation of control antibody (isotype-matched control hamster IgG) did not induce apoptosis of epithelial cells or pulmonary fibrosis. The expression of TGF-
mRNA was upregulated from day 7 to day 28 in lung tissues of anti-Fas antibody-treated mice but not in those of control mice. In this report,
we present the evidence that repeated inhalation of anti-Fas antibody mimicking Fas-Fas ligand cross-linking induces excessive apoptosis and inflammation, which results in pulmonary fibrosis in mice.
| |
Introduction |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Although apoptosis has been implicated as a homeostatic mechanism, it may play a role in human diseases in two different ways. First, diseases may be caused by a malfunction of the apoptosis mechanism. Repair after an acute lung injury requires the elimination of proliferating mesenchymal and inflammatory cells from the alveolar airspace or alveolar walls (1, 2). Failure to clear unwanted cells by apoptosis will prolong the inflammation because of the release of their toxic contents. Second, excessive apoptosis may cause disease. An injection of monoclonal anti-Fas antibody (Jo2) into adult mice caused hepatic failure and death (3), suggesting that acute fulminant hepatitis in humans may be caused by apoptosis mediated by Fas antigen (Fas).
Fas antigen is a cell surface protein that mediates apoptosis. It is expressed in various cells and tissues including the thymus, liver, ovary, heart, and lung. It shares structural homology with a number of cell surface receptors, including tumor necrosis factor receptor and nerve growth factor receptor (4). Mice carrying the lymphoproliferative (lpr) mutation have defects in the Fas antigen gene (5). The lpr mice develop lymphadenopathy and suffer from a systemic lupus erythematosus-like autoimmune disease, indicating an important role for Fas antigen in the negative selection of autoreactive T cells in the thymus (1).
Damage to and the loss of epithelial cells are commonly seen in acute lung injury and also in chronic fibrosing alveolitis. The acute pulmonary toxicity induced by bleomycin in vivo leads to DNA damage (6), which is known to induce apoptosis in vitro (7, 8). We previously found the incidence of apoptosis, Fas mRNA expression in alveolar epithelial cells, and Fas ligand (FasL) mRNA expression in infiltrating lymphocytes in a mouse model of bleomycin-induced pulmonary fibrosis (9). FasL in the physiologic cell death mechanism has a short half-life and may act only at a short distance when it is present at a sufficiently high concentration (10). In bleomycin-induced pulmonary fibrosis, FasL mRNA was continuously and excessively expressed in infiltrating lymphocytes (9). Therefore, we hypothesized that excessive apoptosis mediated by overexpression of FasL may induce pulmonary fibrosis. In this study, we investigated whether continuous inhalation of anti-Fas antibody can induce excessive and chronic apoptosis in bronchiolar and alveolar epithelial cells, which leads to pulmonary fibrosis in mice.
Tumor necrosis factor 
(TNF-) promotes inflammation, cell migration, and proliferation. TNF- mRNA and
protein have been detected in lungs from patients with idiopathic pulmonary fibrosis (11) and in lungs from mice with
pulmonary fibrosis induced by bleomycin (12). Miyazaki
and coworkers demonstrated that pulmonary fibrosis progressed in TNF- transgenic mice (13). Transforming growth
factor (TGF-) is unique in its widespread actions that
enhance the deposition of extracellular matrix. In the
model of pulmonary fibrosis induced by bleomycin, total
lung TGF- mRNA (14) and protein content (15) were
higher than those in normal mice, and the increased production of TGF- preceded the synthesis of collagens, fibronectin, and proteoglycans (16). In immunohistochemical study, TGF- was observed in bronchiolar epithelial
cells of patients with advanced idiopathic pulmonary fibrosis (17). Therefore, we also assessed the expression of TNF- and TGF- mRNA in this model.
| |
Materials and Methods |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
Mice and Anti-Fas Antibody Treatment
In these experiments, 6-week old ICR mice were divided into three groups. The first and second groups consisted of control mice, treated with saline only (n = 40) or with isotype-matched control hamster IgG antibody (n = 40) (Organon Teknika Co., Durham, NC), respectively. The third group (n = 80) was treated with anti-mouse Fas monoclonal antibody (JO-2) (Pharmingen, San Diego, CA). Following measurement of body weight, mice were put in a chamber and allowed to inhale 10 ml of an aerosolized anti-Fas antibody (1 or 10 µg/ml in saline), hamster IgG antibody (20 µg/ml), or saline for only 30 min. After inhalation, mice were returned to their cages and allowed food and water ad libitum. This treatment was continued for 2 weeks every other day. Mice (n = 8 per each time point) were anesthetized 6 h, or 1, 7, 14, or 28 d, after the inhalation and prepared for bronchoalveolar lavage (BAL) (n = 3), light microscopy and electron microscopy (n = 2), or RNA extraction and hydroxyproline measurement (n = 3).
Bronchoalveolar Lavage
The animals were anesthetized with an intraperitoneal injection of sodium pentobarbital (Dinabot Co., Osaka, Japan) either 6 h, or 1, 7, 14, or 28 d, after inhalation. After thoracotomy, the lungs were explored. Following insertion of a tracheal tube, BAL was performed through the cannulated tube with 5 ml of sterile saline at room temperature. The recovered fluid was filtered through a single layer of gauze to remove mucus. Cells in the lavage fluid were counted using a hemocytometer. Differential counts were performed on a total of 100 cells stained with Diff-Quick (Baxter Diagnostics, Düdingen, Switzerland).
Histology of the Lung
After thoracotomy, the pulmonary circulation was flushed with saline, and the lungs were explored. After sacrifice, the lung samples were inflated with 10% formalin solution instilled at 15 cm H2O pressure through the trachea for 2 h and fixed with buffered 10% formalin solution for 24 h. After embedding in paraffin, the sections were prepared and stained with hematoxylin and eosin, and Elastica-Van Gieson staining was performed.
Electron Microscopy
For electron microscopy, the anti-Fas antibody-treated mice were killed on day 14 after the anti-Fas antibody inhalation, and lungs were fixed with 2.5% glutaraldehyde in 0.1 M phosphate buffer, pH 7.4, for 18 h. The lungs were dissected into small pieces and postfixed for 1.5 h in 1% OsO4 dissolved in 0.1 M phosphate buffer (pH 7.4), then dehydrated through a series of graded ethanol solutions and embedded in Epon. Ultrathin sections were cut, stained with uranyl acetate and lead nitrate, and examined under a JEM-1200 EX transmission electron microscope (JEOL Co., Tokyo, Japan).
DNA Nick End Labeling of Tissue Sections
TdT-mediated dUTP-biotin nick end labeling (TUNEL) was performed according to the protocols described by Gavrieli and coworkers (18) with slight modifications (9).
Hydroxyproline Assay
The animals inhaled anti-Fas antibody (Jo2) at 1 or 10 µg/ ml, isotype-matched control hamster IgG at 20 µg/ml in saline, or saline alone for 30 min every other day for 2 weeks. The animals were anesthetized with an intraperitoneal injection of sodium pentobarbital on day 1, 7, 14, or 28. The lungs were frozen in liquid nitrogen, lyophilized (Lyph Lock 12; Labconco, Kansas City, MO), weighed, and minced to a fine homogeneous mixture. Lung tissue was hydrolyzed in 6 M HCl for 16 h at 120°C. The hydroxyproline content of each sample was determined according to the protocols of Woessner (19).
RNA Preparation and Analysis
Total RNA was prepared from lung tissues by use of an Isogen RNA extraction kit (Nippon Gene, Tokyo, Japan). For the polymerase chain reaction (PCR) analysis of RNA, cDNA was prepared by reverse transcription (RT) of 4 µg of each RNA sample in a 20-µl reaction volume containing 10 mM Tris-HCl (pH 8.8), 50 mM KCl, 4 mM MgCl2, 0.1% Triton X-100, 1 mM dithiothreitol (DTT), 0.25 mM dNTPs, 5 µM random hexamer primers, 0.1 U/µl of ribonuclease inhibitor (Promega Corp., Madison, WI), and 10 U/µl of Moloney murine leukemia virus reverse transcriptase (Mo-MuLV-RT) (GIBCO-BRL, Gaithersburg, MD). The reaction mixture was incubated at 42°C for 1 h, and at 95°C for 5 min. The cDNAs were then diluted to 100 µl, and these cDNAs were used in all PCRs. The PCR amplifications were performed in a 50-µl reaction volume containing 5 µg of each cDNA, 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 2.5 mM MgCl2, 0.1% Triton X-100, 0.2 mM dNTPs, and 1.25 U of Taq polymerase (Nippon Gene). The primers and probes used were as follows:
-actin:
Sense 5'-TCCTGTGGCATCCATGAAACT-3'
Antisense 5'-CTTCGTGAACGCCACGTGCTA-3'
Probe 5'-GGAGATTACTGCTCTGGCTC-3'
TGF-:
Sense 5'-ACCATCCATGACATGAACCG-3'
Antisense 5'-TCCCAGACAGAAGTTGGCAT-3'
Probe 5'-TTCAGCTCCACAGAGAAGAACTGC-3'
TNF-:
Sense 5'-GGCAGGTCTACTTTGGAGTCATTGC-3'
Antisense 5'-ACATTCGAGGCTCCAGTGAA-3'
Probe 5'-TATGGCTCAGAGTCCAACTC-3'
The conditions for amplification were as follows: -actin,
TGF-, TNF-; 93°C for 3 min for 1 cycle, 93°C for 1 min,
63°C for 1 min, 72°C for 2 min for 35 cycles, and 72°C for 7 min for 1 cycle. Cycle curve studies confirmed that, for the
amounts of cDNA being amplified, the reactions had not
reached the plateau of the amplification curve at 35 cycles
for any primer pair. Negative controls performed with no
RT yielded no detectable fragments with either primer pair.
PCR products for TGF-, TNF-, and -actin cDNA were
transferred to Hybond-N hybridization transfer membranes (Amersham, Arlington Heights, IL). The membrane was
hybridized with an oligonucleotide probe labeled with
digoxigenin-ddUTP using the DIG oligonucleotide 3'-end
labeling kit (Boehringer Mannheim Biochemicals, Indianapolis, IN). The hybridizations were performed according to manufacturer recommendations. The digoxigenin-labeled probe that hybridized with the PCR products was
detected with the DIG nucleic acid detection kit (Boehringer Mannheim).
Statistical Analysis
To determine statistical significance, a Student's t test for nonpaired data was performed and values of P < 0.05 and P < 0.01 were considered significant.
| |
Results |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
BAL Fluid Cell Analysis
Figure 1 shows that the number of total cells, macrophages, neutrophils, and lymphocytes in BAL fluid (BALF) were significantly increased on day 7 in anti-Fas antibody-treated mice compared to control IgG-treated mice (**P < 0.01, *P < 0.05). It should be stressed that the number of lymphocytes was still significantly increased on day 14, and even on day 28 compared to control mice, whereas neutrophils rapidly disappeared from BALF by day 14. There was no change in BALF cell population in saline-treated mice.
|
Microscopic Findings in Mouse Lung
Figure 2 shows representative histologic findings in this model. On day 1, inflammatory cells infiltrated only the area surrounding the bronchioles (Figure 2A). By day 7, alveolar walls were thickened with edema and infiltrated with neutrophils and mononuclear cells (Figure 2B). After 14 days, the alveolar septa were infiltrated with lymphocytes and plasma cells (Figure 2C). After 28 days, a large number of lymphocytes infiltrated into the interstitium, and proliferation of fibroblasts was observed (Figures 2D and 2E). There were only minimal changes in isotype-matched control antibody-treated mice on day 14 (Figure 2F). On day 28, Elastica-Van Gieson staining showed the deposition of microfibrils in thickened alveolar walls, and fibroblast accumulation in areas where alveolar spaces had collapsed (Figures 2G and 2H).
|
DNA Fragmentation Analysis of Lung Tissue
Localization of DNA fragmentation was determined by TUNEL. TUNEL demonstrated positive signals in nuclei of bronchiolar epithelial cells on day 1 after anti-Fas antibody inhalation (Figure 3A). These signals were continued until day 28. In addition, positive signals were also found in nuclei of alveolar epithelial cells surrounding the bronchioles and signal distribution was gradually expanded to the whole lung field from day 1 to 14 (Figure 3B); these signals had resolved by day 28.
|
Electron Microscopic Findings
Electron microscopic findings confirmed the presence of apototic nuclei in bronchiolar and alveolar epithelial cells. Bronchiolar epithelial cells, particularly Clara cells, contained condensed and fragmented nuclei. Chromatin condensation was also found in the nuclei of alveolar epithelial cells (Figure 4). These epithelial cells presented many vacuoles in their cytoplasm. Although typical morphological features of apoptosis were observed in only 12 of 240 (5%) epithelial cells, chromatin condensation and variously sized cytoplasmic vacuoles were detected in as many as 144 of 240 (60%) epithelial cells. Inhalation of control antibody or saline alone did not induce apoptosis or nuclear changes in epithelial cells.
|
Hydroxyproline Assay
To quantitate the deposition of collagen, lung tissue was treated with acid and the hydroxyproline content was determined. There was a significant increase in lung hydroxyproline content in mice treated with 1 or 10 µg/ml anti-Fas antibody (day 14 [P < 0.05]; day 28 [1 µg/ml, P < 0.05; 10 µg/ml, P < 0.01]), compared with mice treated with control antibody or saline (Figure 5). There was also a significant difference in lung hydroxyproline content by day 28 between 1- and 10-µg/ml anti-Fas antibody-treated mice (P < 0.05).
|
Cytokine Gene Expression
The expression of TGF- mRNA was upregulated in anti-Fas antibody-treated mice from day 1 to day 28, especially
from day 7 to day 28, but not in mice treated with control
antibody. TNF- mRNA were upregulated from day 1 to
day 7 in both groups (Figure 6).
|
| |
Discussion |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
The control of cell number is determined by a balance between cell proliferation and cell death. Although physiologic cell death occurs primarily through an evolutionarily conserved form of cell suicide termed apoptosis, excessive apoptosis may lead to a failure to clear the apoptotic cells, which results in the amplification of inflammation by released cell contents. Fas is abundantly expressed not only in the liver, but also in the heart and lungs. The primary cells from these tissues are sensitive to Fas-mediated apoptosis (20). It is possible that an abnormally activated Fas- FasL system plays a role in human disease. Hepatocytes transformed with human hepatitis C virus (4) express virus antigens and activate cytotoxic T cells to express FasL, which then bind to Fas on hepatocytes, inducing them to undergo apoptosis. This process normally occurs in the removal of virus-infected cells, but excessive apoptosis may lead to fulminant hepatitis.
We previously demonstrated that Fas mRNA was expressed in bronchiolar and alveolar epithelial cells and Fas ligand mRNA was upregulated in infiltrating lymphocytes in bleomycin-induced pulmonary fibrosis in mice (9). Therefore, we investigated whether Fas-FasL cross-linking can lead to pulmonary fibrosis. In this study, the repeated inhalation of anti-Fas antibody induced apoptosis of bronchiolar and alveolar epithelial cells and pulmonary fibrosis. On day 1, positive TUNEL signals were observed mainly in bronchiolar epithelial cells and in some alveolar epithelial cells around the bronchioles. On day 14, these signals of alveolar epithelial cells became evident and diffuse. It is possible that inhaled anti-Fas antibody was trapped mostly in the bronchioles, but that some antibodies reached the alveolar space. The repeated inhalation of antibody and infiltrating inflammatory cells caused DNA strand breaks in alveolar epithelial cells. The localization of TUNEL-positive signals was compatible with the localization of Fas mRNA in mice as previously described (9). The electron microscopic findings confirmed apoptotic changes in these cells (Figure 4). Analysis of hydroxyproline contents and microscopic findings demonstrated the proliferation of fibroblasts and the collagen deposition in lung tissues. These results demonstrated that excessive apoptosis caused by the Fas-FasL system can induce infiltration of inflammatory cells and pulmonary fibrosis in mice.
There is some evidence that the presence of an intact epithelial cell layer directly controls fibroblast proliferation (21, 22). Studies on the repopulation of denuded tracheal explants by epithelial cells showed that the denuded tracheal implants fill rapidly with fibroblasts, unless enough epithelial cells are introduced into the lumen to control fibroblast proliferation (21). Alternatively, epithelial cells may control the proliferation of fibroblasts by releasing cytokines that downregulate fibroblast activity. Therefore, it is possible that excessive apoptosis of epithelial cells may induce the proliferation of fibroblasts through the loss of inhibitory function against fibroblast proliferation. In polycystic human kidneys, it also has been demonstrated that apoptotic nuclei can be detected in noncystic tubular epithelial cells, but not in kidneys from normal humans (23). This suggests that apoptosis may be associated with the progressive loss of renal tissue in polycystic kidney disease, which may lead to secondary interstitial fibrosis.
In this study, we also demonstrated the kinetics of two
key cytokines (TGF- and TNF-) that were detected in a
number of animal models of fibrosis and in pulmonary fibrosis of human. TGF- mRNA was upregulated in anti-Fas antibody-treated mice, especially from day 7 to day 28. In contrast, TNF- mRNA was upregulated in the early
phase (from day 1 to day 7) after treatment. The kinetic
study on the appearance of TNF- and TGF- showed
that there was an induction of TNF- in the early phase,
presumably monocyte derived, and subsequently TGF-
was increased in a rat model of bleomycin-induced pulmonary fibrosis (24). TGF- was observed using immunohistochemistry (17) in bronchiolar epithelial cells in lung tissues from patients with advanced idiopathic pulmonary fibrosis. The kinetics of these cytokines in the Fas antibody-induced fibrosis model seemed similar to those in
the bleomycin-induced model. In addition, Abreu and coworkers demonstrated that Fas-Fas antibody ligation can
lead to production of interleukin 8 by colonic epithelial
cells in vitro, which represents another function mediated by Fas in addition to apoptosis (25). This result suggests
that unknown functions of the anti-Fas antibody, other
than causing apoptosis, may induce new gene expression.
It should be determined whether anti-Fas antibody cross-linking can induce the expression of TGF- and other cytokines in bronchiolar and alveolar epithelial cells and in
macrophages in vitro.
In conclusion, repeated inhalation of anti-Fas antibody mimicking Fas-FasL cross-linking resulted in excessive cell death of epithelial cells, which seemed to overwhelm the clearing mechanism necessary to maintain homeostasis. This condition may prolong the inflammation and interfere with re-epithelialization, which results in the overgrowth of mesenchymal cells. We have demonstrated here that the excessive apoptosis caused by anti-Fas antibody cross-linking leads to persistent inflammation and pulmonary fibrosis.
| |
Footnotes |
|---|
Abbreviations: Fas ligand, FasL; lymphoproliferative mutation, lpr; transforming growth factor , TGF-; tumor necrosis factor , TNF-; TdT-mediated dUTP-biotin nick end labeling, TUNEL.
(Received in original form January 8, 1997 and in revised form May 19, 1997).
Acknowledgments: The authors would like to thank Miss Kyoko Hirano for her expert technical assistance with electron microscopy.
| |
References |
|---|
|
Top
Abstract
Introduction
Materials & Methods
Results
Discussion
References
|
|---|
1. Cox, G., J. Crossley, and Z. Xing. 1995. Macrophage engulfment of apoptotic neutrophils contributes to the resolution of acute pulmonary inflammation in vivo. Am. J. Respir. Cell Mol. Biol. 12: 232-237 [Abstract].
2. Polnovsky, V. A., B. Chen, C. Henke, D. Snover, C. Wendt, D. H. Ingbar, and P. B. Bitterman. 1993. Role of mesenchymal cell death in lung remodeling after injury. J. Clin. Invest. 92: 388-397 .
3. Ogasawara, J., R. Watanabe-Fukunaga, M. Adachi, A. Matsuzawa, T. Kasugai, Y. Kitamura, N. Itoh, T. Suda, and S. Nagata. 1993. Lethal effect of the anti-Fas antibody in mice. Nature (London) 364: 806-809 [Medline].
4. Hisamitsu, N., N. Hayashi, K. Katayama, K. Mochizuki, Y. Kawanishi, A. Kasahara, H. Fusamoto, and T. Kamada. 1994. Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C. Hepatology 19: 1354-1359 [Medline].
5. Watanabe-Fukunaga, R., C. I. Brannan, N. G. Copeland, N. A. Jenkins, and S. Nagata. 1992. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature (London) 356: 314-317 [Medline].
6. Harrison, J. H. Jr., D. G. Hoyt, and J. S. Lazo. 1989. Acute pulmonary toxicity of bleomycin: DNA scission and matrix protein mRNA levels in bleomycin-sensitive and -resistant strains of mice. Mol. Pharmacol. 36: 231-238 [Abstract].
7.
Omar, T.,
P. Geraldine,
J. Belehradek Jr., and
M. Lluis.
1993.
Bleomycin, an apoptosis-mimetic drug that induces two types of cell death depending
on the number of molecules internalized.
Cancer Res.
53:
5462-5469
8. Margalet, V., M. Lucus, F. Solano, and R. Goberna. 1993. Sensitivity of insulin-secreting RIN m5F cells to undergoing apoptosis by the protein kinase C inhibitor staurosporine. Exp. Cell Res. 209: 160-163 [Medline].
9. Hagimoto, N., K. Kuwano, Y. Nomoto, R. Kunitake, and N. Hara. 1997. Apoptosis and expression of Fas/Fas ligand mRNA in bleomycin-induced pulmonary fibrosis in mice. Am. J. Respir. Cell Mol. Biol. 16: 91-101 [Abstract].
10. Dhein, J., H. Walczak, C. Bäumler, K. M. Debatin, and P. H. Krammer. 1995. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95). Nature (London) 373: 438-441 [Medline].
11. Nash, J. R., P. J. McLaughlin, D. Butcher, and B. Corrin. 1993. Expression of tumor necrosis factor-alpha in cryptogenic fibrosing alveolitis. Histopathology 22: 343-347 [Medline].
12.
Piguet, P. F.,
M. A. Collart,
G. E. Grau,
Y. Kapanci, and
P. Vassalli.
1989.
Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis.
J. Exp. Med.
170:
655-663
13. Miyazaki, Y., K. Araki, C. Vesin, I. Garcia, Y. Kapanci, J. A. Whitsett, P. F. Piguet, and P. Vassalli. 1995. Expression of a tumor necrosis factor-alpha transgene in murine lung causes lymphocytic and fibrosing alveolitis: a mouse model of progressive pulmonary fibrosis. J. Clin. Invest. 96: 250-259 .
14. Raghow, B., P. Irish, and A. H. Kang. 1989. Coordinate regulation of transforming growth factor beta gene expression and cell proliferation in hamster lungs undergoing bleomycin-induced pulmonary fibrosis. J. Clin. Invest. 84: 1836-1842 .
15.
Khalil, N.,
O. Bereznay,
M. Sporn, and
A. H. Greenberg.
1989.
Macrophage
production of transforming growth factor beta and fibroblast collagen synthesis in chronic pulmonary inflammation.
J. Exp. Med.
170:
727-737
16.
Hoyt, D. G., and
J. S. Lazo.
1988.
Alterations in pulmonary mRNA encoding procollagens, fibronectin and transforming growth factor-beta precede
bleomycin-induced pulmonary fibrosis in mice.
J. Pharmacol. Exp. Ther.
246:
765-771
17. Khalil, N., R. N. O'Connor, H. W. Unruh, P. W. Warren, K. C. Flanders, A. Kemp, O. H. Bereznay, and A. H. Greenberg. 1991. Increased production and immunohistochemical localization of transforming growth factor-beta in idiopathic pulmonary fibrosis. Am. J. Respir. Cell Mol. Biol. 5: 155-162 .
18.
Gavrieli, Y.,
Y. Sherman, and
S. A. Ben-Sasson.
1992.
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
J. Cell Biol.
119:
493-501
19. Woessner, J. F.. 1961. The determination of hydroxyproline in tissue and protein samples containing small proportions of this amino acid. Arch. Biochem. Biophys. 93: 440-447 [Medline].
20. Itoh, N., S. Yonehara, A. Ishii, M. Yonehara, S. Mizushima, M. Sameshima, A. Hase, Y. Seto, and S. Nagata. 1991. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell 66: 233-243 [Medline].
21.
Terzaghi, M.,
P. Nettesheim, and
M. L. Williams.
1978.
Repopulation of denuded tracheal grafts with normal, preneoplastic and neoplastic epithelial cell populations.
Cancer Res.
38:
4546-4553
22. Adamson, I. Y.. 1992. Relationship of mesenchymal changes to alveolar epithelial cell differentiation in fetal rat lung. Anat. Embryol. 185: 275-280 [Medline].
23.
Woo, D..
1995.
Apoptosis and loss of renal tissue in polycystic kidney diseases [see comments].
N. Engl. J. Med.
333:
18-25
24. Phan, S. H., and S. L. Kunkel. 1992. Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp. Lung Res. 18: 29-43 [Medline].
25.
Abreu, M. M.,
A. Vidrich,
D. H. Lynch, and
S. R. Targan.
1995.
Divergent induction of apoptosis and IL-8 secretion in HT-29 cells in response to
TNF-lpha and ligation of Fas antigen.
J. Immunol.
155:
4147-4154
[Abstract].
This article has been cited by other articles:
 |
|
 |
|
  M. Mouded, E. E. Egea, M. J. Brown, S. M. Hanlon, A. M. Houghton, L. W. Tsai, E. P. Ingenito, and S. D. Shapiro Epithelial Cell Apoptosis Causes Acute Lung Injury Masquerading as Emphysema Am. J. Respir. Cell Mol. Biol., October 1, 2009; 41(4): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. MacRedmond, G. K. Singhera, and D. R. Dorscheid Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury Eur. Respir. J., June 1, 2009; 33(6): 1403 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Drakopanagiotakis, A. Xifteri, V. Polychronopoulos, and D. Bouros Apoptosis in lung injury and fibrosis Eur. Respir. J., December 1, 2008; 32(6): 1631 - 1638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Stowell, C. M. Arthur, K. A. Slanina, J. R. Horton, D. F. Smith, and R. D. Cummings Dimeric Galectin-8 Induces Phosphatidylserine Exposure in Leukocytes through Polylactosamine Recognition by the C-terminal Domain J. Biol. Chem., July 18, 2008; 283(29): 20547 - 20559. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kurosu, Y. Takiguchi, O. Okada, N. Yumoto, S. Sakao, Y. Tada, Y. Kasahara, N. Tanabe, K. Tatsumi, M. Weiden, et al. Identification of Annexin 1 as a Novel Autoantigen in Acute Exacerbation of Idiopathic Pulmonary Fibrosis J. Immunol., July 1, 2008; 181(1): 756 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. De Paepe, S. Gundavarapu, U. Tantravahi, J. R. Pepperell, S. A. Haley, F. I. Luks, and Q. Mao Fas-Ligand-Induced Apoptosis of Respiratory Epithelial Cells Causes Disruption of Postcanalicular Alveolar Development Am. J. Pathol., July 1, 2008; 173(1): 42 - 56. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kisseleva and D. A. Brenner Fibrogenesis of Parenchymal Organs Proceedings of the ATS, April 15, 2008; 5(3): 338 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kisseleva and D. A. Brenner Mechanisms of Fibrogenesis Experimental Biology and Medicine, February 1, 2008; 233(2): 109 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A Beamer and A. Holian Antigen-Presenting Cell Population Dynamics during Murine Silicosis Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 729 - 738. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Matute-Bello, M. M. Wurfel, J. S. Lee, D. R. Park, C. W. Frevert, D. K. Madtes, S. D. Shapiro, and T. R. Martin Essential Role of MMP-12 in Fas-Induced Lung Fibrosis Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 210 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. R. Young, R. Pasula, P. M. Gulleman, G. H. Deutsch, and F. X. McCormack Susceptibility of Hermansky-Pudlak Mice to Bleomycin-Induced Type II Cell Apoptosis and Fibrosis Am. J. Respir. Cell Mol. Biol., July 1, 2007; 37(1): 67 - 74. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Vyas-Read, P. W. Shaul, I. S. Yuhanna, and B. C. Willis Nitric oxide attenuates epithelial-mesenchymal transition in alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L212 - L221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Golan-Gerstl, S. B. Wallach-Dayan, G. Amir, and R. Breuer Epithelial Cell Apoptosis by Fas Ligand-Positive Myofibroblasts in Lung Fibrosis Am. J. Respir. Cell Mol. Biol., March 1, 2007; 36(3): 270 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. R. Stowell, S. Karmakar, C. J. Stowell, M. Dias-Baruffi, R. P. McEver, and R. D. Cummings Human galectin-1, -2, and -4 induce surface exposure of phosphatidylserine in activated human neutrophils but not in activated T cells Blood, January 1, 2007; 109(1): 219 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Lee, H.-R. Kang, R. J. Homer, G. Chupp, and J. A. Elias Transgenic Modeling of Transforming Growth Factor-{beta}1: Role of Apoptosis in Fibrosis and Alveolar Remodeling. Proceedings of the ATS, July 1, 2006; 3(5): 418 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Otsuki, Y. Miura, Y. Nishimura, F. Hyodoh, A. Takata, M. Kusaka, H. Katsuyama, M. Tomita, A. Ueki, and T. Kishimoto Alterations of Fas and Fas-Related Molecules in Patients with Silicosis. Experimental Biology and Medicine, May 1, 2006; 231(5): 522 - 533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Wallach-Dayan, G. Izbicki, P. Y. Cohen, R. Gerstl-Golan, A. Fine, and R. Breuer Bleomycin initiates apoptosis of lung epithelial cells by ROS but not by Fas/FasL pathway Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L790 - L796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. R. S. Budinger, G. M. Mutlu, J. Eisenbart, A. C. Fuller, A. A. Bellmeyer, C. M. Baker, M. Wilson, K. Ridge, T. A. Barrett, V. Y. Lee, et al. Proapoptotic Bid is required for pulmonary fibrosis PNAS, March 21, 2006; 103(12): 4604 - 4609. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. J. Thannickal and J. C. Horowitz Evolving concepts of apoptosis in idiopathic pulmonary fibrosis. Proceedings of the ATS, January 1, 2006; 3(4): 350 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. R. Martin, N. Hagimoto, M. Nakamura, and G. Matute-Bello Apoptosis and Epithelial Injury in the Lungs Proceedings of the ATS, October 1, 2005; 2(3): 214 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Y. Lee, C. Schroedl, J. K. Brunelle, L. J. Buccellato, O. I. Akinci, H. Kaneto, C. Snyder, J. Eisenbart, G. R. S. Budinger, and N. S. Chandel Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L521 - L528. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. De Paepe, Q. Mao, Y. Chao, J. L. Powell, L. P. Rubin, and S. Sharma Hyperoxia-induced apoptosis and Fas/FasL expression in lung epithelial cells Am J Physiol Lung Cell Mol Physiol, October 1, 2005; 289(4): L647 - L659. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Matute-Bello, J. S. Lee, W. C. Liles, C. W. Frevert, S. Mongovin, V. Wong, K. Ballman, S. Sutlief, and T. R. Martin Fas-Mediated Acute Lung Injury Requires Fas Expression on Nonmyeloid Cells of the Lung J. Immunol., September 15, 2005; 175(6): 4069 - 4075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chen, Z. Tong, Q. Ye, S. Nakamura, U. Costabel, and J. Guzman Expression of tumour necrosis factor receptors by bronchoalveolar cells in hypersensitivity pneumonitis Eur. Respir. J., June 1, 2005; 25(6): 1039 - 1043. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Genovese, E. Mazzon, R. D. Paola, C. Muia, M. D. Threadgill, A. P. Caputi, C. Thiemermann, and S. Cuzzocrea Inhibitors of Poly(ADP-Ribose) Polymerase Modulate Signal Transduction Pathways and the Development of Bleomycin-Induced Lung Injury J. Pharmacol. Exp. Ther., May 1, 2005; 313(2): 529 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Krick, B. G. Eul, J. Hanze, R. Savai, F. Grimminger, W. Seeger, and F. Rose Role of Hypoxia-Inducible Factor-1{alpha} in Hypoxia-Induced Apoptosis of Primary Alveolar Epithelial Type II Cells Am. J. Respir. Cell Mol. Biol., May 1, 2005; 32(5): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hodge, G. Hodge, M. Holmes, and P. N. Reynolds Increased airway epithelial and T-cell apoptosis in COPD remains despite smoking cessation Eur. Respir. J., March 1, 2005; 25(3): 447 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Neff, R.-F. Guo, S. B. Neff, J. V. Sarma, C. L. Speyer, H. Gao, K. D. Bernacki, M. Huber-Lang, S. McGuire, L. M. Hoesel, et al. Relationship of Acute Lung Inflammatory Injury to Fas/FasL System Am. J. Pathol., March 1, 2005; 166(3): 685 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Plataki, A. V. Koutsopoulos, K. Darivianaki, G. Delides, N. M. Siafakas, and D. Bouros Expression of Apoptotic and Antiapoptotic Markers in Epithelial Cells in Idiopathic Pulmonary Fibrosis Chest, January 1, 2005; 127(1): 266 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bao, Y. Wang, P. Sweeney, A. Chaudhuri, A. I. Doseff, C. B. Marsh, and D. L. Knoell Keratinocyte growth factor induces Akt kinase activity and inhibits Fas-mediated apoptosis in A549 lung epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L36 - L42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Chen, Y.-W. Chang, C.-W. Yao, T.-S. Chiueh, S.-C. Huang, K.-Y. Chien, A. Chen, F.-Y. Chang, C.-H. Wong, and Y.-J. Chen Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry PNAS, December 7, 2004; 101(49): 17039 - 17044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H Miyazaki, K Kuwano, K Yoshida, T Maeyama, M Yoshimi, M Fujita, N Hagimoto, R Yoshida, and Y Nakanishi The perforin mediated apoptotic pathway in lung injury and fibrosis J. Clin. Pathol., December 1, 2004; 57(12): 1292 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Li, R. Shu, G. Filippatos, and B. D. Uhal Apoptosis in lung injury and remodeling J Appl Physiol, October 1, 2004; 97(4): 1535 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. De Paepe, Q. Mao, M. Embree-Ku, L. P. Rubin, and F. I. Luks Fas/FasL-mediated apoptosis in perinatal murine lungs Am J Physiol Lung Cell Mol Physiol, October 1, 2004; 287(4): L730 - L742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Undevia, D. R. Dorscheid, B. A. Marroquin, W. L. Gugliotta, R. Tse, and S. R. White Smad and p38-MAPK signaling mediates apoptotic effects of transforming growth factor-{beta}1 in human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, September 1, 2004; 287(3): L515 - L524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Nadrous, J. H. Ryu, W. W. Douglas, P. A. Decker, and E. J. Olson Impact of Angiotensin-Converting Enzyme Inhibitors and Statins on Survival in Idiopathic Pulmonary Fibrosis Chest, August 1, 2004; 126(2): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Scholz, A. Simon, M. Berg, A. M. Schuller, M. Hacibayramoglu, S. Margraf, A. Theisen, J. Windolf, G. Wimmer-Greinecker, and A. Moritz In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: Arterial in-line application in a porcine cardiac surgery model J. Thorac. Cardiovasc. Surg., June 1, 2004; 127(6): 1735 - 1742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nakamura, G. Matute-Bello, W. C. Liles, S. Hayashi, O. Kajikawa, S.-M. Lin, C. W. Frevert, and T. R. Martin Differential Response of Human Lung Epithelial Cells to Fas-Induced Apoptosis Am. J. Pathol., June 1, 2004; 164(6): 1949 - 1958. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mori, H. Morishita, H. Nakamura, H. Matsuoka, K. Yoshida, Y. Kishima, Z. Zhou, H. Kida, T. Funakoshi, S. Goya, et al. Hepatoma-Derived Growth Factor Is Involved in Lung Remodeling by Stimulating Epithelial Growth Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 459 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Hart, K. M. Alexander, and I. Dransfield Immune Complexes Bind Preferentially to Fc{gamma}RIIA (CD32) on Apoptotic Neutrophils, Leading to Augmented Phagocytosis by Macrophages and Release of Proinflammatory Cytokines J. Immunol., February 1, 2004; 172(3): 1882 - 1887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Lesur, M. Brisebois, A. Thibodeau, F. Chagnon, D. Lane, and T. Fullop Role of IFN-{gamma} and IL-2 in rat lung epithelial cell migration and apoptosis after oxidant injury Am J Physiol Lung Cell Mol Physiol, January 1, 2004; 286(1): L4 - L14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, H. Rayford, and B. D. Uhal Essential Roles for Angiotensin Receptor AT1a in Bleomycin-Induced Apoptosis and Lung Fibrosis in Mice Am. J. Pathol., December 1, 2003; 163(6): 2523 - 2530. [Abstract] [Full Text]
|
|
|
|
|
|
V. Ruiz, R. Ma. Ordonez, J. Berumen, R. Ramirez, B. Uhal, C. Becerril, A. Pardo, and M. Selman Unbalanced collagenases/TIMP-1 expression and epithelial apoptosis in experimental lung fibrosis Am J Physiol Lung Cell Mol Physiol, November 1, 2003; 285(5): L1026 - L1036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.D. Uhal Epithelial apoptosis in the initiation of lung fibrosis Eur. Respir. J., September 20, 2003; 22(44_suppl): 7s - 9s. [Full Text] [PDF]
|
|
|
|
|
|
V. E. Kagan, G. G. Borisenko, B. F. Serinkan, Y. Y. Tyurina, V. A. Tyurin, J. Jiang, S. X. Liu, A. A. Shvedova, J. P. Fabisiak, W. Uthaisang, et al. Appetizing rancidity of apoptotic cells for macrophages: oxidation, externalization, and recognition of phosphatidylserine Am J Physiol Lung Cell Mol Physiol, July 1, 2003; 285(1): L1 - L17. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Hart, C. Jackson, L. M. Kremmel, M. S. McNeill, H. Jersmann, K. M. Alexander, J. A. Ross, and I. Dransfield Specific Binding of an Antigen-Antibody Complex to Apoptotic Human Neutrophils Am. J. Pathol., March 1, 2003; 162(3): 1011 - 1018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Li, H. Zhang, V. Soledad-Conrad, J. Zhuang, and B. D. Uhal Bleomycin-induced apoptosis of alveolar epithelial cells requires angiotensin synthesis de novo Am J Physiol Lung Cell Mol Physiol, March 1, 2003; 284(3): L501 - L507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Renshaw, J. S. Parmar, V. Singleton, S. J. Rowe, D. H. Dockrell, S. K. Dower, C. D. Bingle, E. R. Chilvers, and M. K. B. Whyte Acceleration of Human Neutrophil Apoptosis by TRAIL J. Immunol., January 15, 2003; 170(2): 1027 - 1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Fujita, M. Maruyama, J. Araya, K. Sassa, Y. Kawagishi, R. Hayashi, S. Matsui, T. Kashii, N. Yamashita, E. Sugiyama, et al. Hydrogen Peroxide Induces Upregulation of Fas in Human Airway Epithelial Cells via the Activation of PARP-p53 Pathway Am. J. Respir. Cell Mol. Biol., November 1, 2002; 27(5): 542 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. H. Albertine, M. F. Soulier, Z. Wang, A. Ishizaka, S. Hashimoto, G. A. Zimmerman, M. A. Matthay, and L. B. Ware Fas and Fas Ligand Are Up-Regulated in Pulmonary Edema Fluid and Lung Tissue of Patients with Acute Lung Injury and the Acute Respiratory Distress Syndrome Am. J. Pathol., November 1, 2002; 161(5): 1783 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Tanaka, M. Yoshimi, T. Maeyama, N. Hagimoto, K. Kuwano, and N. Hara Resistance to Fas-mediated apoptosis in human lung fibroblast Eur. Respir. J., August 1, 2002; 20(2): 359 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. G. Crystal, P. B. Bitterman, B. Mossman, M. I. Schwarz, D. Sheppard, L. Almasy, H. A. Chapman, S. L. Friedman, T. E. King Jr., L. A. Leinwand, et al. Future Research Directions in Idiopathic Pulmonary Fibrosis: Summary of a National Heart, Lung, and Blood Institute Working Group Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 236 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Matsuoka, T. Arai, M. Mori, S. Goya, H. Kida, H. Morishita, H. Fujiwara, I. Tachibana, T. Osaki, and S. Hayashi A p38 MAPK inhibitor, FR-167653, ameliorates murine bleomycin-induced pulmonary fibrosis Am J Physiol Lung Cell Mol Physiol, July 1, 2002; 283(1): L103 - L112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hagimoto, K. Kuwano, I. Inoshima, M. Yoshimi, N. Nakamura, M. Fujita, T. Maeyama, and N. Hara TGF-{beta}1 as an Enhancer of Fas-Mediated Apoptosis of Lung Epithelial Cells J. Immunol., June 15, 2002; 168(12): 6470 - 6478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R. Coulter, A. Doseff, P. Sweeney, Y. Wang, C. B. Marsh, M. D. Wewers, and D. L. Knoell Opposing Effect by Cytokines on Fas-Mediated Apoptosis in A549 Lung Epithelial Cells Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 58 - 66. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Barazzone Argiroffo, Y. R. Donati, J. Boccard, A. F. Rochat, C. Vesin, C.-D. Kan, and P.-F. Piguet CD40-CD40 Ligand Disruption Does Not Prevent Hyperoxia-Induced Injury Am. J. Pathol., January 1, 2002; 160(1): 67 - 71. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Hotchkiss, W. M. Dunne, P. E. Swanson, C. G. Davis, K. W. Tinsley, K. C. Chang, T. G. Buchman, I. E. Karl, H. Grassme, S. Kirschnek, et al. Role of Apoptosis in Pseudomonas aeruginosa Pneumonia Science, November 30, 2001; 294(5548): 1783a - 1783. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Matute-Bello, C. W. Frevert, W. C. Liles, M. Nakamura, J. T. Ruzinski, K. Ballman, V. A. Wong, C. Vathanaprida, and T. R. Martin Fas/Fas Ligand System Mediates Epithelial Injury, but Not Pulmonary Host Defenses, in Response to Inhaled Bacteria Infect. Immun., September 1, 2001; 69(9): 5768 - 5776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Dincer, N. Gangopadhyay, R. Wang, and B. D. Uhal Norepinephrine induces alveolar epithelial apoptosis mediated by {alpha}-, {beta}-, and angiotensin receptor activation Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L624 - L630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Uhal Fas and apoptosis in the alveolar epithelium: holes in the dike? Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L326 - L327. [Full Text] [PDF]
|
|
|
|
|
|
G. Matute-Bello, W. C. Liles, C. W. Frevert, M. Nakamura, K. Ballman, C. Vathanaprida, P. A. Kiener, and T. R. Martin Recombinant human Fas ligand induces alveolar epithelial cell apoptosis and lung injury in rabbits Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L328 - L335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. EICKELBERG, A. PANSKY, E. KOEHLER, M. BIHL, M. TAMM, P. HILDEBRAND, A. P. PERRUCHOUD, M. KASHGARIAN, and M. ROTH Molecular mechanisms of TGF-{beta} antagonism by interferon {gamma} and cyclosporine A in lung fibroblasts FASEB J, March 1, 2001; 15(3): 797 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. KITAMURA, S. HASHIMOTO, N. MIZUTA, A. KOBAYASHI, K. KOOGUCHI, I. FUJIWARA, and H. NAKAJIMA Fas/FasL-dependent Apoptosis of Alveolar Cells after Lipopolysaccharide-induced Lung Injury in Mice Am. J. Respir. Crit. Care Med., March 1, 2001; 163(3): 762 - 769. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Serrao, J. D. Fortenberry, M. L. Owens, F. L. Harris, and L. A. S. Brown Neutrophils induce apoptosis of lung epithelial cells via release of soluble Fas ligand Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L298 - L305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Matute-Bello, R. K. Winn, M. Jonas, E. Y. Chi, T. R. Martin, and W. C. Liles Fas (CD95) Induces Alveolar Epithelial Cell Apoptosis in Vivo : Implications for Acute Pulmonary Inflammation Am. J. Pathol., January 1, 2001; 158(1): 153 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Q. Truong-Tran, R. E. Ruffin, and P. D. Zalewski Visualization of labile zinc and its role in apoptosis of primary airway epithelial cells and cell lines Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1172 - L1183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. De Paepe, L. P. Rubin, C. Jude, A. M. Lesieur-Brooks, D. R. Mills, and F. I. Luks Fas ligand expression coincides with alveolar cell apoptosis in late-gestation fetal lung development Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L967 - L976. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Fine, Y. Janssen-Heininger, R. P. Soultanakis, S. G. Swisher, and B. D. Uhal Apoptosis in lung pathophysiology Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L423 - L427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. AOSHIBA, S. YASUI, J. TAMAOKI, and A. NAGAI The Fas/Fas-Ligand System Is Not Required for Bleomycin-induced Pulmonary Fibrosis in Mice Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 695 - 700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang, O. Ibarra-Sunga, L. Verlinski, R. Pick, and B. D. Uhal Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L143 - L151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.A. D. Cooper Jr. Pulmonary Fibrosis . Pathways Are Slowly Coming into Light Am. J. Respir. Cell Mol. Biol., May 1, 2000; 22(5): 520 - 523. [Full Text]
|
|
|
|
|
|
R. Bargout, A. Jankov, E. Dincer, R. Wang, T. Komodromos, O. Ibarra-Sunga, G. Filippatos, and B. D. Uhal Amiodarone induces apoptosis of human and rat alveolar epithelial cells in vitro Am J Physiol Lung Cell Mol Physiol, May 1, 2000; 278(5): L1039 - L1044. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kuwano and N. Hara Signal Transduction Pathways of Apoptosis and Inflammation Induced by the Tumor Necrosis Factor Receptor Family Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 147 - 149. [Full Text]
|
|
|
|
|
|
R. Wang, C. Ramos, I. Joshi, A. Zagariya, A. Pardo, M. Selman, and B. D. Uhal Human lung myofibroblast-derived inducers of alveolar epithelial apoptosis identified as angiotensin peptides Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1158 - L1164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Wang, A. Zagariya, E. Ang, O. Ibarra-Sunga, and B. D. Uhal Fas-induced apoptosis of alveolar epithelial cells requires ANG II generation and receptor interaction Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1245 - L1250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Zanella, C. R. Timblin, A. Cummins, M. Jung, J. Goldberg, R. Raabe, T. R. Tritton, and B. T. Mossman Asbestos-induced phosphorylation of epidermal growth factor receptor is linked to c-fos and apoptosis Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L684 - L693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Hagimoto, K. Kuwano, M. Kawasaki, M. Yoshimi, Y. Kaneko, R. Kunitake, T. Maeyama, T. Tanaka, and N. Hara Induction of Interleukin-8 Secretion and Apoptosis in Bronchiolar Epithelial Cells by Fas Ligation Am. J. Respir. Cell Mol. Biol., September 1, 1999; 21(3): 436 - 445. [Abstract] [Full Text]
|
|
|
|
 |
|
 G. Filippatos, C. Leche, R. Sunga, A. Tsoukas, P. Anthopoulos, I. Joshi, A. Bifero, R. Pick, and B. D. Uhal Expression of FAS adjacent to fibrotic foci in the failing human heart is not associated with increased apoptosis Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H445 - H451. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. N. Liu, A. Z. Mohammed, W. R. Rice, D. T. Fiedeldey, J. S. Liebermann, J. A. Whitsett, T. J. Braciale, and R. I. Enelow Perforin-Independent CD8+ T-Cell-Mediated Cytotoxicity of Alveolar Epithelial Cells Is Preferentially Mediated by Tumor Necrosis Factor-alpha . Relative Insensitivity to Fas Ligand Am. J. Respir. Cell Mol. Biol., May 1, 1999; 20(5): 849 - 858. [Abstract] [Full Text]
|
|
|
|
|
|
R. Wang, A. Zagariya, O. Ibarra-Sunga, C. Gidea, E. Ang, S. Deshmukh, G. Chaudhary, J. Baraboutis, G. Filippatos, and B. D. Uhal Angiotensin II induces apoptosis in human and rat alveolar epithelial cells Am J Physiol Lung Cell Mol Physiol, May 1, 1999; 276(5): L885 - L889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Berthiaume, O. Lesur, and A. Dagenais Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium Thorax, February 1, 1999; 54(2): 150 - 160. [Full Text]
|
|
|
|
|
|
K. Kuwano, H. Miyazaki, N. Hagimoto, M. Kawasaki, M. Fujita, R. Kunitake, Y. Kaneko, and N. Hara The Involvement of Fas-Fas Ligand Pathway in Fibrosing Lung Diseases Am. J. Respir. Cell Mol. Biol., January 1, 1999; 20(1): 53 - 60. [Abstract] [Full Text]
|
|
|
|
|
|
N. Hussain, F. Wu, L. Zhu, R. S. Thrall, and M. J. Kresch Neutrophil Apoptosis during the Development and Resolution of Oleic Acid-Induced Acute Lung Injury in the Rat Am. J. Respir. Cell Mol. Biol., December 1, 1998; 19(6): 867 - 874. [Abstract] [Full Text]
|
|
|
|
|
|
B. D. Uhal, I. Joshi, W. F. Hughes, C. Ramos, A. Pardo, and M. Selman Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung Am J Physiol Lung Cell Mol Physiol, December 1, 1998; 275(6): L1192 - L1199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Uhal, C. Gidea, R. Bargout, A. Bifero, O. Ibarra-Sunga, M. Papp, K. Flynn, and G. Filippatos Captopril inhibits apoptosis in human lung epithelial cells: a potential antifibrotic mechanism Am J Physiol Lung Cell Mol Physiol, November 1, 1998; 275(5): L1013 - L1017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Barazzone, S. Horowitz, Y. R. Donati, I. Rodriguez, and P.-F. Piguet Oxygen Toxicity in Mouse Lung: Pathways to Cell Death Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 573 - 581. [Abstract] [Full Text]
|
|
|
|
|
|
P. M. Yao and I. Tabas Free Cholesterol Loading of Macrophages Induces Apoptosis Involving the Fas Pathway J. Biol. Chem., July 28, 2000; 275(31): 23807 - 23813. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Proc. Am. Thorac. Soc. | Am. J. Respir. Crit. Care Med. |