Effect of IgA on Respiratory Burst and Cytokine Release by Human Alveolar Macrophages
| Autor: | Jean-Pierre Vaerman, Charles Pilette, Yves Sibille, Youssef Ouadrhiri, Renato C. Monteiro |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Pulmonary and Respiratory Medicine MAPK/ERK pathway Lipopolysaccharide medicine.medical_treatment Clinical Biochemistry Receptors Fc In Vitro Techniques Biology chemistry.chemical_compound Downregulation and upregulation Antigens CD Macrophages Alveolar medicine Humans Receptor Molecular Biology Respiratory Burst Kinase Cell Biology Macrophage Activation Molecular biology Immunoglobulin A Up-Regulation Respiratory burst Cytokine chemistry Biochemistry Carcinogens Tetradecanoylphorbol Acetate Phosphorylation Mitogen-Activated Protein Kinases Signal Transduction |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 26:315-332 |
| ISSN: | 1535-4989 1044-1549 |
| Popis: | Human alveolar macrophages (HAM) express FcalphaR 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 Fc(alpha)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-kappaB (NF-kappaB) in HAM, we evaluate the effect of IgA on NF-kappaB. Treatment of HAM with LPS, p- and S-IgA, but not PMA, induces NF-kappaB activation through IkappaBalpha phosphorylation and subsequent proteolysis. Antioxidants, namely N-acetylcysteine (NAC) and glutathione (GSH), have no effects on IgA-mediated NF-kappaB 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-kappaB. TNF-alpha release by LPS-activated HAM is sensitive to NF-kappaB 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-kappaB. Our results show a differential HAM regulation by IgA through both dependent and independent modulation of ERK pathway. In addition, IgA activates NF-kappaB and this effect was independent on oxidants. These data may help to understand the role of IgA in both lung protection and inflammation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|