| Summary: | 碩士 === 國立陽明大學 === 微生物及免疫學研究所 === 97 === The complement system plays important roles in innate immune responses against infectious microbes. It is under cascade activation immediately upon infection. The complement component C5 was cleaved into C5a and C5b after activation. The small fragment C5a activates immune cells, such as neutrophils and macrophages, and enhances inflammatory responses. Two types of C5a receptors, C5aR and C5L2, have been reported. Both of them belong to the GPCR family. Under C5a stimulation, C5aR transduces signals through G-protein and activates immune cells. C5L2, lacking the G-protein coupling DRY domain, was originally thought as a non-functional decoy receptor. However, recent studies showed that C5L2 plays important roles in C5a-mediated immune responses. The mechanism about how C5L2 participates C5a signaling still remains unclear. Many GPCRs mediate their signals by forming multi-molecular receptor complex. We speculate that C5L2 and C5aR may mediate C5a-induced signals by forming multi-recptor complex. In this study, we first confirmed that C5aR expression on C5L2 deficient bone marrow neutrophil surface is dramaticly diminished. Surface C5aR level is altered by increasing C5L2 expression in C5aR-overexpressed stable 293T transfectants. C5L2-C5aR interaction was determined by biochemical co-immunopreciptation experiment. The colocalization of C5aR and C5L2 was then monitored by con-focal microscopy observation. The molecular interaction between C5aR and C5L2 was further confirmed by the fluorescence resonance energy transfer (FRET) analysis. Whether this interaction dedicates the C5a-mediated signaling still remains an interesting question and will be further determined comprehensively. Taken together, we reveal a novel mechanism that C5L2 could modulate C5a-mediated signaling through the molecular interaction with C5aR.
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