Interleukin-4 augments production of the third complement component by the alveolar epithelial cell line A549.
The elements of allergic inflammation and the involvement of helper T lymphocytes are increasingly being recognized in the immunopathogenesis of asthma. Allergen exposure leading to the activation of allergen-specific T cells present in the lung can result in the release of cytokines which in turn can locally stimulate the cellular constituents of the lung. The airway epithelial cells may be the key participants in such an interaction. Therefore, we examined the ability of T-cell-derived IL-4 to modulate the production of C3 and C5 by the human type-II pneumocyte cell line A549, which is known to produce all the components and the regulatory proteins of the complement system. For estimation of C3 an ELISA detecting native C3 was used. Following stimulation of A549 with hrIL-4 a dose-dependent (1-50 U/ml) enhancement of C3 production was observed, which reached its maximum (5-fold of unstimulated cells) at 48 h and gradually declined thereafter. Concentrations of hrIL-4 higher than 50 U/ml did not further increase C3 production. In parallel experiments hrIFN-gamma at concentrations between 10 and 50 U/ml stimulated the C3 production to more than twice the quiescent state level within 24 h. In the pneumocyte cell line A549 we demonstrated the expression of a gene for the IL-4 receptor which appears to mediate the biological effect of this lymphokine. A diminution in the functionally active C5, estimated by ELISA at the same time, was observed in supernatants of A549 cultures following stimulation with hrIL-4 as well as with hrIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)
Khirwadkar
K
K
Institut für Immunologie, Universität Heidelberg, BRD.
Zilow
G
G
Oppermann
M
M
Kabelitz
D
D
Rother
K
K
D002460:Cell Line; D003176:Complement C3 / Q000096:biosynthesis*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology
D003176:Complement C3; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma