巨噬细胞集落刺激因子与血管平滑肌细胞增殖

Macrophage colony stimulating factor and vascular smooth muscle cell proliferation

目的一些以血管平滑肌细胞（ＶＳＭＣ）增殖为特点的血管疾病，在病变部位常有巨噬细胞浸润。本研究巨噬细胞集落刺激因子（ＭＣＳＦ）在ＶＳＭＣ生长调节中的作用。方法实验采用培养大鼠主动脉ＶＳＭＣ，细胞增殖观察指标采用氚标胸腺嘧啶核苷掺入法，并用Ｎｏｒｔｈｅｒｎｂｌｏｔ技术测定原癌基因表达。结果（１）Ｌ９２９细胞上清液（富含ＭＣＳＦ）及重组ＭＣＳＦ以剂量依赖关系刺激氚标胸腺嘧啶核苷掺入；（２）ＶＳＭＣ在接受刺激后表达某些原癌基因，如ｃｆｏｓ、ｃｍｙｃ、ｅｒｇ１和ＪｕｎＢ；（３）凝血酶、ＰＤＧＦ、ｂＦＧＦ与ＭＣＳＦ在促增殖作用上具有协同作用。结论ＭＣＳＦ与其它生长因子协同作用，通过自分泌／旁分泌机制调控ＶＳＭＣ增殖。

Objective In several vascular diseases an abnormal vascular smooth cell (VSMC) proliferation is often associated with the presence of macrophages. we examined whether macrophage colony stimulating factor (MCSF) might play a role in the control of VSMC growth. Methods Cultured rat VSMC were obtained from thoracic aortae. Cell proliferation was evaluated by measuring thymidine incorporation and by determing proto oncogene expression assessed with Northern blot analysis. Results Our results showed that (1) The addition of L929 cell supernatant (a rich source of MCSF) or of recombinant MCSF promoted DNA synthesis in a concentration dependent manner, an effect that could be abrogated by the presence of a specific anti MCSF antibody. (2) The addition of L929 supernatant induced of c fos, c myc, egr 1 and junB expression. (3) It was further demonstrated that MCSF acted in synergy with thrombin, platelet derived growth factor (PDGF) or basic fibroblast growth factor (bFGF) in promoting VSMC growth. Conclusion These data suggest that in concert with other growth factors MCSF affects the growth of cultured VSMC through autocrine/paracrine mechanisms. These effects confer to MCSF an important role in the development of vascular lesion formation.