血小板因子4对巨核细胞的保护作用及其在肿瘤化疗中的意义

Protective effect of platelelt factor 4 and on megakaryocytesand its potential applications in chemotherapy

目的：研究血小板因子４对造血细胞的保护作用及其机制。方法：用液体或半固体培养法及流式细胞术测定血小板因子４对ＣＤ３４阳性脐血细胞的增殖与分化的作用。结果：血小板因子４可逆性地抑制ＣＤ３４阳性细胞向巨核细胞的发育。这种抑制可保留更多的巨核系干细胞并使其对５氟尿嘧啶具有更强的抗性。血小板因子４还可抑制由血小板生成素诱导的巨核细胞生长。结论：血小板因子４通过调控血小板生成素的作用而使一些巨核细胞祖细胞保持在发育的早期阶段，这些细胞具有较高增殖潜力并对细胞周期特异性化疗药物相对不敏感。

Objective: To provide evidence for understanding the effect and mechanism of platelet factor 4 (PF4) on hematopoietic cells.Methods: Liquid and semi solid culture systems as well as flow cytometry were used to study the effect of PF4 on the proliferation and differentiation of CD34+ cord blood cells. Results: In vitro development of the megakaryocytic progenitor cells from CD34+ cord blood cells was inhibited by PF4 in a reversible manner. When this reversible inhibition was abolished, the cells exhibited a more significant population of megakaryocytic progenitor cells which was more resistant against cytotoxic agent 5 fluorouracil than control. On the other hand, PF4 inhibited the growth of megakaryocyte induced by recombinant thrombopoietin. Conclusions: PF4 exerted its inhibitory effect by regulating the action of thrombopoietin and the reversibility of PF4 inhibition allowed some megakaryocytic progenitor cells to be retained in more primitive stages at which the cells possess a higher potential for proliferation and are relatively less sensitive to the cell cycle specific cytotoxic agents. Therefore, PF4 should be a potent protective agent of megakaryocytopoiesis and thrombocytopoiesis during chemotherapy.