Monocyte chemotactic protein‐1 as a chemoattractant for human hepatic stellate cells

摘要: Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown regulate leukocyte trafficking by secreting monocyte protein-1 (MCP-1), a chemokine that recruits monocytes lymphocytes. In this study, we explored whether MCP-1 exerts biological actions on HSC. were isolated from normal human livers, cultured plastic, studied their myofibroblast-like phenotype, three different lines used. Chemotaxis was measured modified Boyden chambers. Phosphatidylinositol 3-kinase (PI 3-K) assayed phosphotyrosine immunoprecipitates. Exposure of stimulated migration dose-dependent fashion. Maximal stimulation obtained with 250 ng/mL MCP-1, which resulted 3- 4-fold cell migration. Checkerboard analysis showed the increase almost completely result chemotaxis rather than chemokinesis. contrast, quiescent HSC, did not exert any effect leukocytes, activates pertussis toxin-sensitive CCR2 receptor. However, transcripts for could be toxin only modestly inhibited MCP-1-induced associated an cytosolic calcium concentration, PI 3-K activity, protein tyrosine phosphorylation. Blocking influx or pretreatment inhibitor wortmannin markedly reduced This study shows, first time, potential direct profibrogenic action via chemotaxis. MCP-1-dependent signals these are transduced may mediated alternative receptors. (HEPATOLOGY 1999;29:140-148.)