血小板第4因子抑制巨核细胞系膜结合型c-kit的表达(英文)

Platelet Factor 4 Inhibits Membrane-Bound c-kit Expression in Megakaryocytic Cell Lines

细胞表面受体c-kit与干细胞因子(SCF)对维持血细胞的生成起重要作用。血小板第4因子(PF4)能特异性地抑制巨核细胞生成。在本实验中研究了PF4对两个巨核细胞系HEL和Dami的c-kit表达影响。结果显示,经PF4处理的两株细胞,其c-kit mRNA表达量均下降,细胞表面受体数量降低,SCF与c-kit的结合量亦下降,两组差异有显著意义。在对细胞膜CD34表达影响方面,PF4与TGFβ1的作用相反,PF4促进CD34的表达,而TGFβ1抑制CD34的表达。研究表明,PF4抑制巨核细胞生长的机理,部分途径可能是通过抑制c-kit/SCF而产生。

The cell surface receptor c-kit and its ligand or stem cell factor (SCF) are important for the maintenance of hematopoiesis both in vivo and in vitro. Platelet factor 4 (PF4) has been shown to be a specific lineage inhibitor of megakaryocytopoiesis. In this study, we examined the effect of PF4 on the expression of mRNA and membrane-bound c-kit on two megakaryocytic cell lines, HEL and Dami. Both megakaryocytic cell lines constitutively expressed c-kit on the cell surface. Treatment of these cell lines with PF4 resulted in a downregulation of c-kit mRNA, cell surface expression of c-kit and an inhibition of SCF binding to c-kit. PF4 inhibition was dose-dependent. TGFβl also downregulated the expression of c-kit. However, the effect of PF4 and TGFβ1 on CD34 expression was opposite. TGFβ1 downregulated, while PF4 upregulated CD34 expression. This study provides evidence that PF4 may act negatively on megakaryocytic cell growth at least in part by decreasing SCF/c-kit interaction in megakaryocytic cell lines.