PubMed1999
We previously reported that a 21-kDa phosphoprotein may play an important role in superoxide production through dephosphorylation by neutrophillike differentiated HL-60 cells (Suzuki et al., 1995, Biochim Biophys Acta 1266: 261-267). The phosphoprotein was identified as cofilin, an actin-binding protein, and the activation-induced changes in its intracellular distribution have been described elsewhere (Suzuki et al., 1995, J Biol Chem 270:19551-19556). However, the physiologic roles of cofilin in phagocytes remain to be established, and the regulatory mechanisms for dephosphorylation and translocation of cofilin are unknown. In the present study, we investigated the roles of cofilin in the opsonized zymosan (OZ)-activated macrophagelike U937 cells by using herbimycin A, an inhibitor for protein tyrosine kinase. In the individual adherent phagocytes, OZ induced many events: 1) production of superoxide, 2) phagocytosis of the insoluble particles OZ, 3) dephosphorylation of cofilin, 4) translocation of cofilin from cytosol to plasma membrane regions, 5) decrease in intracellular pH from 7.4 to aprroximately 6.8, and 6) rapid and transient increase in filamentous actin at the cell periphery. All of these events were inhibited or reduced significantly by herbimycin A. OZ increased phosphorylation of tyrosine in 110-, 50-, 34-, and 29-kDa proteins, whereas herbimycin A inhibited it. These results suggest that tyrosine kinase plays an essential role upstream of these events through phosphorylation of such proteins. Furthermore, microinjection of anti-cofilin antibody to the differentiated U937 cells caused inhibition of the phagocytosis. These results suggest that cofilin plays critical roles in phagocytic functions through changes in cytoskeletal organization.
Actin Depolymerizing Factors↗