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 microM). 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 (CD11b) 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.
Chiou
Wen Fei
WF
National Research Institute of Chinese Medicine, No. 155-1, Li-Nung Street Section 2, Shih-Pai, 112, Taipei, Taiwan. wfchiou@cma23.nricm.edu.tw
Yau-Chik Shum
Andrew
A
Peng
Chuen Huei
CH
Chen
Chieh Fu
CF
Chou
Cheng Jen
CJ
D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D039481:CD11b Antigen / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002633:Chemotaxis / Q000187:drug effects; D003078:Colchicine / Q000494:pharmacology; D015936:Complement C5a / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007769:Lactams / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D011554:Pseudopodia / Q000187:drug effects* / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D018821:CD18 Antigens; D007769:Lactams; C415282:piperlactam S; D003571:Cytochalasin B; D015936:Complement C5a; D020764:cdc42 GTP-Binding Protein; D003078:Colchicine