Xi X, Caen J P, Fournier S, Schlegel N, Amiral J, Sibony O, Blot P, Han Z C
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
Br J Haematol. 1996 May;93(2):265-72. doi: 10.1046/j.1365-2141.1996.4901032.x.
Mechanisms of the action of platelet factor 4 (PF4) on the growth of megakaryocyte (MK) progenitor cells in CD34+ cord blood (CB) cells were studied in comparison with transforming growth factor beta1 (TGFbeta1). Development of MK from CD34+ CB cells in both plasma clot culture and liquid culture was significantly inhibited by either purified human PF4 and by recombinant human TGFbeta1. Inhibition of MK colony formation by PF4 was reversible because CD34+ cells preincubated with PF4 could regenerate colonies after washing and replating into secondary cultures. In contrast, TGFbeta1-preincubated CD34+ cells gave rise to few colonies following replating. Moreover, incubation of CD34+ cells with PF4 in liquid culture caused the increased number of both stem cell factor (SCF)-binding cells and CD34 antigen-bearing cells. In addition, PF4-preincubated CD34+ cells exhibited a higher potential in MK colony formation in the presence of 5-fluorouracil (5FU). These results demonstrate that both PF4 and TGFbeta1 inhibit MK development from CD34+ CB cells by different mechanisms, and suggest that PF4, unlike TGFbeta1, exerts its inhibitory effect on the growth of the target cells in a reversible manner which results in a preservation of a more immature and 5FU-resistant cell population.
与转化生长因子β1（TGFβ1）相比，研究了血小板因子4（PF4）对CD34 +脐血（CB）细胞中巨核细胞（MK）祖细胞生长的作用机制。在血浆凝块培养和液体培养中，纯化的人PF4和重组人TGFβ1均显著抑制了CD34 + CB细胞中MK的发育。PF4对MK集落形成的抑制作用是可逆的，因为预先用PF4孵育的CD34 +细胞在洗涤并重新接种到二次培养物中后可以再生集落。相比之下，预先用TGFβ1孵育的CD34 +细胞重新接种后产生的集落很少。此外，在液体培养中将CD34 +细胞与PF4一起孵育会导致干细胞因子（SCF）结合细胞和携带CD34抗原的细胞数量增加。此外，预先用PF4孵育的CD34 +细胞在存在5-氟尿嘧啶（5FU）的情况下在MK集落形成中表现出更高的潜力。这些结果表明，PF4和TGFβ1均通过不同机制抑制CD34 + CB细胞中MK的发育，并表明PF4与TGFβ1不同，以可逆方式对靶细胞的生长发挥抑制作用，从而保留了更不成熟且对5FU耐药的细胞群体。
