| Summary: | 碩士 === 長庚大學 === 天然藥物研究所 === 94 === Cytochalasin B (CB), an actin disrupting agent derived from fungi, has been suggested that it potentiates the effects of chemoattractants such as ROS production, aggregation, and degranulation in neutrophils. However, we do not know whether CB potentiates fMLP-induced MAC-1 expression. In present study, we demonstrated that CB potentiated fMLP-induced Mac-1 expression in human neutrophils. This effect can be inhibited by pretreatment of jasplakinolide (a stabilizer of filamentous actin) , colchicine (a degranulation inhibitor), BDM (a endosome recycling inhibitor), SB203580 (a p38 inhibitor), wortmannin (a PI3K inhibitor), genistein (a tyrosine kinase inhibitor), and pertussis toxin (a G-protein coupled receptor inhibitor) but not BAPTA (a calcium chealater), PD98059 (an erk 1/2 inhibitor), staurosporine (a PKC inhibitor), and superoxide dismutase (SOD), suggested multiple signal transduction pathway and granule release involved in this process. CB markedly increased intracellular calcium level and enhanced phosphorylation of tyrosine, erk 1/2, p38, and Akt caused by fMLP. In addition, the deactivated formyl peptide receptor (FPR) can be reactivated by CB and this effect can be inhibited by jasplakinolide and colchicine. Surprisingly, F-actin polymerization induced by fMLP was also potentiated by CB and was inhibited by pretreatment of jasplakinolide, colchicine, BDM, SB203580, wortmannin, genistein, and pertussis toxin. In conclusion, the mechanism of CB potentiation of Mac-1 expression induced by fMLP including regulation of FPR reactivation, potentiation of downstream signaling pathway from reactivated receptor, and granule release.
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