期刊
INTERNATIONAL IMMUNOLOGY
卷 20, 期 10, 页码 1239-1245出版社
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxn083
关键词
complement; Fc epsilon RI; mast cell; signal transduction
类别
A peptide with the natural sequence derived from the complement component C3a, designated C3a7, and C3a9, having a modified sequence of that, was previously shown to inhibit the high-affinity IgER (Fc epsilon RI)-induced secretory response of both mucosal and serosal-type mast cells. In addition, several processes that couple the Fc epsilon RI stimulus to the cellular response were all suppressed in the presence of these peptides. Here, we show that peptide C3a9 binds to the Fc epsilon RI on the surface of unperturbed mast cells (rat mucosal-type RBL-2H3 cell line) and remains bound even after Fc epsilon RI-IgE aggregation by antigen as assessed by confocal microscopy. Moreover, that peptide interferes the initial steps of Fc epsilon RI-coupling network. Namely, peptide binding to the Fc epsilon RI beta-chain interrupts this chain's association with both src family protein tyrosine kinases Lyn and Fyn and enhances the internalization of the receptor. C3a9 was further found to inhibit the phosphorylation of two members of the mitogen-activated protein kinase family, extracellular signal-regulated kinase (ERK) and p38. Although ERK is usually activated via the ras-raf-mitogen-activated protein kinase/ERK kinase (MEK) pathway, our results show that C3a9 has no effect on the c-raf phosphorylation, suggesting that this complement-derived peptide inhibits ERK activation via an alternative route. C3a9 also inhibits the late-phase response to Fc epsilon RI stimulus of bone marrow-derived mast cells, reducing secretion of the inflammatory cytokines IL-6 and tumor necrosis factor-alpha. Taken together, the consequence of its interference with the earliest steps of Fc epsilon RI stimulus-response coupling and the C3a-derived peptide inhibits both the immediate and the late-phase responses of mast cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据