Abstract
Phagocytes play a central role in the host defense system. We have previously reported that cofilin, an actin-and PIP2-binding phosphoprotein, is dephosphorylated upon activation of phagocytes. To clarify the role of cofilin in the functions of phagocytes, we investigated the relationship between cofilin and phagocyte activation. In neutrophil-like HL-60 cells, the production of superoxide induced by opsonized zymosan (OZ) was enhanced at l pM and inhibited at 5 pM by okadaic acid (OA), a protein phosphatase inhibitor. Furthermore, OZ induced dephosphorylation and translocation to the plasma membrane regions of cofilin, which were also inhibited by OA at 5μM. In macrophage-like U 937 cells, both Herbimycin A, an inhibitor of Src family tyrosine kinase, and U 73122, an inhibitor of phospholipase C (PLC), inhibited OZ-induced superoxide production and phagocytosis as well as dephosphorylation and translocation of cofilin. Herbimycin A also inhibited the temporary increase of F-actin content, the decrease of intracellular pH, and tyrosine phosphorylation of p 110, p 50, p 34, and p 29, all of which were induced by OZ. In addition, as well as U 73122, Herbimycin A inhibited IP3 production during cell activation by OZ. From these results, it was shown that the activation of phagocytes and the change on the condition of cofilin are significantly related. The signaling pathway from OZ stimulation to cell response including Src family tyrosine kinase and PLC is discussed.
