help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ouadrhiri, Y.
Right arrow Articles by Sibille, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ouadrhiri, Y.
Right arrow Articles by Sibille, Y.

Am. J. Respir. Cell Mol. Biol., Volume 26, Number 3, March, 2002 315-332

Effect of IgA on Respiratory Burst and Cytokine Release by Human Alveolar Macrophages
Role of ERK1/2 Mitogen-Activated Protein Kinases and NF-kappa B

Youssef Ouadrhiri, Charles Pilette, Renato C. Monteiro, Jean-Pierre Vaerman, and Yves Sibille

Experimental Medicine Unit, Christian de Duve Institute of Cellular Pathology, University of Louvain, Brussels, Belgium; and INSERM U25, Necker Hospital, Paris, France

Human alveolar macrophages (HAM) express Fcalpha R receptors for immunoglobulin (Ig)A which could link humoral and cellular branches of lung immunity. Here, we investigate the effects of polymeric (p-IgA) and secretory (S-IgA) IgA interaction with Fcalpha R on lipopolysaccharide (LPS)- and phorbol myristate acetate (PMA)-activated respiratory burst and TNF-alpha release by HAM. Activation of HAM with LPS and PMA increases the respiratory burst and TNF-alpha release through activation of the extracellular signal-related protein kinases 1 and 2 (ERK1/2) pathway, because these effects are inhibited by treatment of HAM with PD98059, a selective inhibitor of mitogen-activated protein (MAP)/ERK kinases (MEK) pathway. S-IgA and p-IgA downregulate the LPS-increased respiratory burst in HAM through an inhibition of ERK1/2 activity. In contrast, p- and S-IgA induce an increase in the respiratory burst of PMA-treated HAM. This effect is associated with an upregulation by IgA of the PMA-induced phosphorylation of ERK1/2 and is also inhibited by PD98059. Moreover, p-IgA and S-IgA enhance TNF-alpha release by HAM through an alternative pathway distinct from ERK1/2. Because LPS is known to activate nuclear factor-kappa B (NF-kappa B) in HAM, we evaluate the effect of IgA on NF-kappa B. Treatment of HAM with LPS, p- and S-IgA, but not PMA, induces NF-kappa B activation through Ikappa Balpha phosphorylation and subsequent proteolysis. Antioxidants, namely N-acetylcysteine (NAC) and glutathione (GSH), have no effects on IgA-mediated NF-kappa B nuclear translocation and only a minor and late effect on that of LPS, suggesting that reactive oxygen intermediates (ROI) play a minor role in HAM activation through NF-kappa B. TNF-alpha release by LPS-activated HAM is sensitive to NF-kappa B inhibition and only partly to oxidant scavenging. In contrast, TNF-alpha release by IgA-treated HAM is not dependent on oxidants and only partly dependent on NF-kappa B. Our results show a differential HAM regulation by IgA through both dependent and independent modulation of ERK pathway. In addition, IgA activates NF-kappa B and this effect was independent on oxidants. These data may help to understand the role of IgA in both lung protection and inflammation.

Abbreviations: antibody(ies), Ab(s); bovine serum albumin, BSA; dichlorofluorescein, DCF; electrohoretic mobility shift assay, EMSA; extracellular protein-related kinase 1 and 2, ERK 1/2; Fc high affinity receptor for IgA, Fcalpha R; fetal calf serum, FCS; flow cytometric analysis, FCA; fluorescein isothiocyanate, FITC; glutathione, GSH; human alveolar macrophages, HAM; horseradish peroxidase, HRP; immunoglobulin, Ig; lipopolysaccharide, LPS; monoclonal Ab, mAb; mitogen-activated protein kinase, MAP kinase; N-acetylcysteine, NAC; nuclear factor-kappa B, NF-kappa B; superoxide anion, O2-; optical density, OD; phospho-specific antibody cell-based ELISA, PACE; phosphate-buffered saline, PBS; PD98059, PD; phosphorylated ERK1/2, pERK1/2; protein kinase C, PKC; phorbol myristate acetate, PMA; phenyl methyl-sulfonyl fluoride, PMSF; phosphorylated p38 MAP kinase, p-p38; respiratory burst, RB; reactive oxygen intermediates, ROI; sheep anti-mouse, SAM; SB203580, SB; swine anti-rabbit, SAR; secretory IgA, S-IgA; tris-buffered saline-tween, TBST; tumor necrosis factor-alpha , TNF-alpha ; WEHI 164 clone 13, WEHI.




This article has been cited by other articles:


Home page
 Nephrol Dial TransplantHome page
J. C. K. Leung, S. C. W. Tang, L. Y. Y. Chan, W. L. Chan, and K. N. Lai
Synthesis of TNF-{alpha} by mesangial cells cultured with polymeric anionic IgA role of MAPK and NF-{kappa}B
Nephrol. Dial. Transplant., January 1, 2008; 23(1): 72 - 81.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. E. Bakema, S. de Haij, C. F. den Hartog-Jager, J. Bakker, G. Vidarsson, M. van Egmond, J. G. J. van de Winkel, and J. H. W. Leusen
Signaling through Mutants of the IgA Receptor CD89 and Consequences for Fc Receptor {gamma}-Chain Interaction
J. Immunol., March 15, 2006; 176(6): 3603 - 3610.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
Y. Wu, S. Adam, L. Hamann, H. Heine, A. J. Ulmer, U. Buwitt-Beckmann, and C. Stamme
Accumulation of Inhibitory {kappa}B-{alpha} as a Mechanism Contributing to the Anti-Inflammatory Effects of Surfactant Protein-A
Am. J. Respir. Cell Mol. Biol., December 1, 2004; 31(6): 587 - 594.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S.-M. Lin, C. W. Frevert, O. Kajikawa, M. M. Wurfel, K. Ballman, S. Mongovin, V. A. Wong, A. Selk, and T. R. Martin
Differential Regulation of Membrane CD14 Expression and Endotoxin-Tolerance in Alveolar Macrophages
Am. J. Respir. Cell Mol. Biol., August 1, 2004; 31(2): 162 - 170.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
C. Pilette, S. R. Durham, J.-P. Vaerman, and Y. Sibille
Mucosal Immunity in Asthma and Chronic Obstructive Pulmonary Disease: A Role for Immunoglobulin A?
Proceedings of the ATS, April 1, 2004; 1(2): 125 - 135.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2002 American Thoracic Society.