C3a-derived peptide binds to the type I FceR and inhibits proximal-coupling signal processes and cytokine secretion by mast cells

摘要: A peptide with the natural sequence derived from complement component C3a, designated C3a7, and C3a9, having a modified of that, was previously shown to inhibit high-affinity IgER (FceRI)induced secretory response both mucosal serosal-type mast cells. In addition, several processes that couple FceRI stimulus cellular were all suppressed in presence these peptides. Here, we show C3a9 binds on surface unperturbed cells (rat mucosaltype RBL-2H3 cell line) remains bound even after FceRI–IgE aggregation by antigen as assessed confocal microscopy. Moreover, interferes initial steps FceRI-coupling network. Namely, binding b-chain interrupts this chain’s association src family protein tyrosine kinases Lyn Fyn enhances internalization receptor. further found phosphorylation two members mitogen-activated kinase family, extracellular signal-regulated (ERK) p38. Although ERK is usually activated via ras–raf–mitogenactivated kinase/ERK (MEK) pathway, our results has no effect c-raf phosphorylation, suggesting complement-derived inhibits activation an alternative route. also late-phase bone marrow-derived cells, reducing secretion inflammatory cytokines IL-6 tumor necrosis factor-a. Taken together, consequence its interference earliest stimulus-response coupling C3a-derived immediate responses