Piperlactam S suppresses macrophage migration by impeding F-actin polymerization and filopodia extension

This study was designed to evaluate the anti-inflammatory effect of piperlactam S on chemoattractant-induced migration, functions underlying leukocyte recruitment in vitro. Results showed that RAW264.7 macrophages migrate toward complement 5a, a powerful chemoattractant for macrophages. This phenomenon could be suppressed concentration dependently by piperlactam S (0.3-30 muM). Fluorescence staining demonstrated that piperlactam S and cytochalasin B both effectively reversed complement 5a-induced cell polarization, filopodia extension, as well as the increase in the cell content of F-actin. Functional inhibition by antibodies suggested that Mac-1 (CD 11b) integrin plays a central role in complement 5a-induced migration. However, piperlactam S failed to modify Mac-1 expression. Furthermore, complement 5a triggered the activation of Cdc42, a Rho-family protein involved in the regulation of filopodia extension, with a time course that paralleled that of filopodia extension and which was inhibited by piperlactam S. In summary, piperlactam S exerts anti-inflammatory effects possibly by interfering with cell migration, impeding F-actin polymerization, filopodia formation, and/or Cdc42 activation. However, the detailed mechanism by which piperlactam S regulates the above processes needs further study. (C) 2002 Elsevier Science B.V. All rights reserved.