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Am. J. Respir. Cell Mol. Biol., Volume 19, Number 4, October, 1998 700-708

Surfactant Protein-A-Deficient Mice Are Susceptible to Pseudomonas aeruginosa Infection

Ann Marie LeVine, Kim E. Kurak, Michael D. Bruno, James M. Stark, Jeffrey A. Whitsett, and Thomas R. Korfhagen

Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio

To determine the role of surfactant protein-A (SP-A) in host defense, the murine SP-A locus was targeted by homologous recombination to produce mice lacking SP-A. SP-A-/- and wild-type mice were infected with mucoid Pseudomonas aeruginosa by intratracheal instillation. Pulmonary bacterial loads were greater in SP-A-/- than in wild-type mice, with increased numbers of mucoid P. aeruginosa in lung homogenates at 6 and 24 h after infection. Pulmonary infiltration with polymorphonuclear leukocytes (PMN) was similar in both groups; however, an earlier influx of PMN into the lung occurred in the SP-A-/- mice. The number of bacteria phagocytosed by alveolar macrophages was decreased in the SP-A-/- mice at 1 h after infection. Superoxide-radical generation by PMN was similar for the SP-A-/- and wild-type mice, but nitrite levels were increased in SP-A-/- mice. Concentrations of tumor necrosis factor-alpha , interleukin-6, and macrophage inflammatory protein-2 (proinflammatory cytokines) were greater in bronchoalveolar lavage fluid at 2 h after infection in SP-A-/- mice. SP-A plays an important role in the pathogenesis of mucoid P. aeruginosa infection in the lung in vivo by enhancing macrophage phagocytosis and clearance of bacteria, and by modifying the inflammatory response.




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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. J. Haley, A. Ciota, J. P. Contreras, M. R. Boothby, D. L. Perkins, and P. W. Finn
Alterations in lung collectins in an adaptive allergic immune response
Am J Physiol Lung Cell Mol Physiol, March 1, 2002; 282(3): L573 - L584.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
S. Murakami, D. Iwaki, H. Mitsuzawa, H. Sano, H. Takahashi, D. R. Voelker, T. Akino, and Y. Kuroki
Surfactant Protein A Inhibits Peptidoglycan-induced Tumor Necrosis Factor-alpha Secretion in U937 Cells and Alveolar Macrophages by Direct Interaction with Toll-like Receptor 2
J. Biol. Chem., February 22, 2002; 277(9): 6830 - 6837.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
K. S. Harrod and R. J. Jaramillo
Pseudomonas aeruginosa and Tumor Necrosis Factor-alpha Attenuate Clara Cell Secretory Protein Promoter Function
Am. J. Respir. Cell Mol. Biol., February 1, 2002; 26(2): 216 - 223.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
O. A. Quintero and J. R. Wright
Clearance of surfactant lipids by neutrophils and macrophages isolated from the acutely inflamed lung
Am J Physiol Lung Cell Mol Physiol, February 1, 2002; 282(2): L330 - L339.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
J. S. Ferguson, D. R. Voelker, J. A. Ufnar, A. J. Dawson, and L. S. Schlesinger
Surfactant Protein D Inhibition of Human Macrophage Uptake of Mycobacterium tuberculosis Is Independent of Bacterial Agglutination
J. Immunol., February 1, 2002; 168(3): 1309 - 1314.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
T. R. Korfhagen
Surfactant Protein A (SP-A)-Mediated Bacterial Clearance . SP-A and Cystic Fibrosis
Am. J. Respir. Cell Mol. Biol., December 1, 2001; 25(6): 668 - 672.
[Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. G. Brinker, E. Martin, P. Borron, E. Mostaghel, C. Doyle, C. V. Harding, and J. R. Wright
Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells
Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1453 - L1463.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
W. T. Watford, J. R. Wright, C. G. Hester, H. Jiang, and M. M. Frank
Surfactant Protein A Regulates Complement Activation
J. Immunol., December 1, 2001; 167(11): 6593 - 6600.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. A. Gutierrez, A. J. Parry, D. M. McMullan, C. J. Chapin, and J. R. Fineman
Decreased surfactant proteins in lambs with pulmonary hypertension secondary to increased blood flow
Am J Physiol Lung Cell Mol Physiol, November 1, 2001; 281(5): L1264 - L1270.
[Abstract] [Full Text] [PDF]

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 Arch Pediatr Adolesc MedHome page
N. Zafar, C. M. Wallace, P. Kieffer, P. Schroeder, M. Schootman, and A. Hamvas
Improving Survival of Vulnerable Infants Increases Neonatal Intensive Care Unit Nosocomial Infection Rate
Arch Pediatr Adolesc Med, October 1, 2001; 155(10): 1098 - 1104.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. M. Hickman-Davis, F. C. Fang, C. Nathan, V. L. Shepherd, D. R. Voelker, and J. R. Wright
Lung surfactant and reactive oxygen-nitrogen species: antimicrobial activity and host-pathogen interactions
Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L517 - L523.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
R. Paananen, R. Sormunen, V. Glumoff, M. van Eijk, and M. Hallman
Surfactant proteins A and D in Eustachian tube epithelium
Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L660 - L667.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. J. Simpson, W. A. H. Wallace, M. E. Marsden, J. R. W. Govan, D. J. Porteous, C. Haslett, and J.-M. Sallenave
Adenoviral Augmentation of Elafin Protects the Lung Against Acute Injury Mediated by Activated Neutrophils and Bacterial Infection
J. Immunol., August 1, 2001; 167(3): 1778 - 1786.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
J. R. Wright, P. Borron, K. G. Brinker, and R. J. Folz
Surfactant Protein A . Regulation of Innate and Adaptive Immune Responses in Lung Inflammation
Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 513 - 517.
[Full Text]

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 Infect. Immun.Home page
M. J. Allen, D. R. Voelker, and R. J. Mason
Interactions of Surfactant Proteins A and D with Saccharomyces cerevisiae and Aspergillus fumigatus
Infect. Immun., April 1, 2001; 69(4): 2037 - 2044.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
T. Madan, U. Kishore, M. Singh, P. Strong, E. M. Hussain, K. B. M. Reid, and P. U. Sarma
Protective Role of Lung Surfactant Protein D in a Murine Model of Invasive Pulmonary Aspergillosis
Infect. Immun., April 1, 2001; 69(4): 2728 - 2731.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Yoshida, M. Ikegami, J. A. Reed, Z. C. Chroneos, and J. A. Whitsett
GM-CSF regulates protein and lipid catabolism by alveolar macrophages
Am J Physiol Lung Cell Mol Physiol, March 1, 2001; 280(3): L379 - L386.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. AWASTHI, J. J. COALSON, B. A. YODER, E. CROUCH, and R. J. KING
Deficiencies in Lung Surfactant Proteins A and D Are Associated with Lung Infection in Very Premature Neonatal Baboons
Am. J. Respir. Crit. Care Med., February 1, 2001; 163(2): 389 - 397.
[Abstract] [Full Text]

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 Infect. Immun.Home page
I. Ofek, A. Mesika, M. Kalina, Y. Keisari, R. Podschun, H. Sahly, D. Chang, D. McGregor, and E. Crouch
Surfactant Protein D Enhances Phagocytosis and Killing of Unencapsulated Phase Variants of Klebsiella pneumoniae
Infect. Immun., January 1, 2001; 69(1): 24 - 33.
[Abstract] [Full Text] [PDF]

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 FASEB J.Home page
K. R. KHUBCHANDANI and J. M. SNYDER
Surfactant protein A (SP-A): the alveolus and beyond
FASEB J, January 1, 2001; 15(1): 59 - 69.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
M. Song and D. S. Phelps
Interaction of Surfactant Protein A with Lipopolysaccharide and Regulation of Inflammatory Cytokines in the THP-1 Monocytic Cell Line
Infect. Immun., December 1, 2000; 68(12): 6611 - 6617.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
H. T. Akinbi, R. Epaud, H. Bhatt, and T. E. Weaver
Bacterial Killing Is Enhanced by Expression of Lysozyme in the Lungs of Transgenic Mice
J. Immunol., November 15, 2000; 165(10): 5760 - 5766.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
A. M. LeVine, J. A. Whitsett, J. A. Gwozdz, T. R. Richardson, J. H. Fisher, M. S. Burhans, and T. R. Korfhagen
Distinct Effects of Surfactant Protein A or D Deficiency During Bacterial Infection on the Lung
J. Immunol., October 1, 2000; 165(7): 3934 - 3940.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
Z. C. Chroneos, S. E. Wert, J. L. Livingston, D. J. Hassett, and J. A. Whitsett
Role of Cystic Fibrosis Transmembrane Conductance Regulator in Pulmonary Clearance of Pseudomonas aeruginosa In Vivo
J. Immunol., October 1, 2000; 165(7): 3941 - 3950.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Hayashida, K. S. Harrod, and J. A. Whitsett
Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection in vivo
Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L452 - L459.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
M. Ikegami, A. H. Jobe, J. Whitsett, and T. Korfhagen
Tolerance of SP-A-deficient mice to hyperoxia or exercise
J Appl Physiol, August 1, 2000; 89(2): 644 - 648.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
L. F. Weikert, J. P. Lopez, R. Abdolrasulnia, Z. C. Chroneos, and V. L. Shepherd
Surfactant protein A enhances mycobacterial killing by rat macrophages through a nitric oxide-dependent pathway
Am J Physiol Lung Cell Mol Physiol, August 1, 2000; 279(2): L216 - L223.
[Abstract] [Full Text] [PDF]

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 ChestHome page
K. C. Meyer, A. Sharma, R. Brown, M. Weatherly, F. R. Moya, J. Lewandoski, and J. J. Zimmerman
Function and Composition of Pulmonary Surfactant and Surfactant-Derived Fatty Acid Profiles Are Altered in Young Adults With Cystic Fibrosis
Chest, July 1, 2000; 118(1): 164 - 174.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. Borron, J. C. McIntosh, T. R. Korfhagen, J. A. Whitsett, J. Taylor, and J. R. Wright
Surfactant-associated protein A inhibits LPS-induced cytokine and nitric oxide production in vivo
Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L840 - L847.
[Abstract] [Full Text] [PDF]

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 J. Immunol.Home page
M. van Eijk, H. P. Haagsman, T. Skinner, A. Archibold, K. B. M. Reid, and P. R. Lawson
Porcine Lung Surfactant Protein D: Complementary DNA Cloning, Chromosomal Localization, and Tissue Distribution
J. Immunol., February 1, 2000; 164(3): 1442 - 1450.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. D. Bruno, T. R. Korfhagen, C. Liu, E. E. Morrisey, and J. A. Whitsett
GATA-6 Activates Transcription of Surfactant Protein A
J. Biol. Chem., January 14, 2000; 275(2): 1043 - 1049.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. E. GREENE, J. R. WRIGHT, K. P. STEINBERG, J. T. RUZINSKI, E. CALDWELL, W. B. WONG, W. HULL, J. A. WHITSETT, T. AKINO, Y. KUROKI, et al.
Serial Changes in Surfactant-associated Proteins in Lung and Serum before and after Onset of ARDS
Am. J. Respir. Crit. Care Med., December 1, 1999; 160(6): 1843 - 1850.
[Abstract] [Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
E. C. Crouch
Modulation of Host-Bacterial Interactions by Collectins
Am. J. Respir. Cell Mol. Biol., November 1, 1999; 21(5): 558 - 561.
[Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
C. I. Restrepo, Q. Dong, J. Savov, W. I. Mariencheck, and J. R. Wright
Surfactant Protein D Stimulates Phagocytosis of Pseudomonas aeruginosa by Alveolar Macrophages
Am. J. Respir. Cell Mol. Biol., November 1, 1999; 21(5): 576 - 585.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W. I. Mariencheck, J. Savov, Q. Dong, M. J. Tino, and J. R. Wright
Surfactant protein A enhances alveolar macrophage phagocytosis of a live, mucoid strain of P. aeruginosa
Am J Physiol Lung Cell Mol Physiol, October 1, 1999; 277(4): L777 - L786.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
M. D. Bruno, J. A. Whitsett, G. F. Ross, and T. R. Korfhagen
Transcriptional Regulation of the Murine Surfactant Protein-A Gene by B-Myb
J. Biol. Chem., September 24, 1999; 274(39): 27523 - 27528.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
M. J. Allen, R. Harbeck, B. Smith, D. R. Voelker, and R. J. Mason
Binding of Rat and Human Surfactant Proteins A and D to Aspergillus fumigatus Conidia
Infect. Immun., September 1, 1999; 67(9): 4563 - 4569.
[Abstract] [Full Text] [PDF]


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