Wolf H M, Hauber I, Gulle H, Samstag A, Fischer M B, Ahmad R U, Eibl M M
Institute of Immunology, University of Vienna, Austria.
Clin Exp Immunol. 1996 Sep;105(3):537-43. doi: 10.1046/j.1365-2249.1996.d01-793.x.
A deregulated expression and/or release of large amounts of inflammatory cytokines such as IL-1 and TNF-alpha accounts for most pathophysiological events in a variety of systemic inflammatory diseases, the effect being mediated by the interaction of these cytokines with their respective receptors. IL-1 receptor antagonist (IL-1Ra), mainly produced by monocytes/macrophages, is an inhibitor of IL-1 activity. The present study shows that human serum IgA induces significant IL-1Ra release in human peripheral blood mononuclear cells and adherent monocytes. IgA induced higher levels of IL-1Ra than Haemophilus influenzae type b (Hib) expressing lipopolysaccharide (LPS), purified LPS or phorbol myristate acetate (PMA), without induction of IL-1 beta release, and even inhibited LPS-induced IL-1 beta release. Induction of IL-1Ra by IgA could be detected both at the mRNA and protein levels in resting and activated monocytes. Ligation of Fc alpha R with MoAb My-43 or treatment with human serum IgA induced protein tyrosine phosphorylation in human monocytes, and herbimycin A, a specific inhibitor of protein tyrosine kinase activity, inhibited IgA-induced IL-1Ra production, suggesting that Fc alpha R-mediated induction of tyrosine phosphorylation is required for the IgA-induced stimulation of IL-1Ra release. In addition, triggering of Fc alpha R with MoAb specifically down-regulated TNF-alpha and IL-6 release in human monocytes activated with Hib. By the induction of IL-1Ra and down-regulation of the release of inflammatory cytokines such as IL-1 beta, TNF-alpha and IL-6, interaction of IgA with human monocytes may actively contribute to the regulation of the inflammatory response.
白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）等大量炎性细胞因子的表达失调和/或释放，是多种全身性炎性疾病中大多数病理生理事件的原因，这些细胞因子与其各自受体的相互作用介导了这种效应。IL-1受体拮抗剂（IL-1Ra）主要由单核细胞/巨噬细胞产生，是IL-1活性的抑制剂。本研究表明，人血清IgA可诱导人外周血单核细胞和贴壁单核细胞释放大量IL-1Ra。与表达脂多糖（LPS）的b型流感嗜血杆菌（Hib）、纯化的LPS或佛波酯肉豆蔻酸酯乙酸酯（PMA）相比，IgA诱导的IL-1Ra水平更高，且不诱导IL-1β释放，甚至抑制LPS诱导的IL-1β释放。在静息和活化的单核细胞中，均可在mRNA和蛋白质水平检测到IgA对IL-1Ra的诱导。用单克隆抗体My-43连接FcαR或用人血清IgA处理可诱导人单核细胞中的蛋白酪氨酸磷酸化，而蛋白酪氨酸激酶活性的特异性抑制剂赫伯霉素A可抑制IgA诱导的IL-1Ra产生，这表明FcαR介导的酪氨酸磷酸化诱导是IgA诱导刺激IL-1Ra释放所必需的。此外，用单克隆抗体触发FcαR可特异性下调用Hib激活的人单核细胞中TNF-α和IL-6的释放。通过诱导IL-1Ra以及下调IL-1β、TNF-α和IL-6等炎性细胞因子的释放，IgA与人单核细胞的相互作用可能积极参与炎症反应的调节。
