Mayani H, Little M T, Dragowska W, Thornbury G, Lansdorp P M
Terry Fox Laboratory, British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
Exp Hematol. 1995 May;23(5):422-7.
We have previously characterized the proliferative response of primitive CD34+ cells, purified from adult bone marrow, umbilical cord blood, and fetal liver, to a mixture of hematopoietic stimulators (steel factor [SF], interleukin-3 [IL-3], IL-6, and erythropoietin [Epo]) in serum-free liquid cultures. In the present study, we assessed the effects of the hematopoietic inhibitors, macrophage inflammatory protein-1 alpha (MIP-1 alpha), transforming growth factor-beta (TGF-beta), and tumor necrosis factor-alpha (TNF-alpha), on the cytokine-induced proliferation of three different CD34+ cell subpopulations derived from cord blood and on total CD34+ cells derived from fetal liver. In cultures of cord blood cells, addition of MIP-1 alpha inhibited the numerical expansion of primitive CD34+ cells (CD34+ CD45RAlow CD71low cells) without inhibiting the proliferation of more mature subpopulations enriched for myeloid (CD34+ CD45RA+ CD71low cells) or erythroid (CD34+ CD45RAlow CD71+ cells) progenitors. TGF-beta significantly reduced the proliferation of all three subpopulations, although its effects were more pronounced on cells of the erythroid lineage, particularly immature erythroid progenitors. Similarly, TNF-alpha preferentially inhibited total nucleated and CD34+ cell production in the subpopulation enriched for erythroid cells. However, in contrast to TGF-beta, TNF-alpha preferentially inhibited the proliferation of more mature erythroid progenitors. In a separate set of experiments, MIP-1 alpha, TGF-beta, and TNF-alpha were added to cultures of total CD34+ cells purified from fetal liver. In keeping with the fact that the majority of the progenitors contained in these cells were erythroid progenitors, the inhibitory effects of the three cytokines were similar to those observed in cultures of CD34+ CD45RAlow CD71+ cord blood cells. The results of the present study demonstrate that MIP-1 alpha, TGF-beta, and TNF-alpha have the capacity to modulate cytokine-induced proliferation of cord blood and fetal liver progenitors. The differential effects of these three cytokines confirm their pleiotropic nature as regulators of hematopoiesis.
我们之前已对从成人骨髓、脐带血和胎儿肝脏中纯化出的原始CD34+细胞在无血清液体培养中对造血刺激因子混合物（钢因子[SF]、白细胞介素-3[IL-3]、IL-6和促红细胞生成素[Epo]）的增殖反应进行了表征。在本研究中，我们评估了造血抑制剂巨噬细胞炎性蛋白-1α（MIP-1α）、转化生长因子-β（TGF-β）和肿瘤坏死因子-α（TNF-α）对源自脐带血的三种不同CD34+细胞亚群以及源自胎儿肝脏的总CD34+细胞的细胞因子诱导增殖的影响。在脐带血细胞培养中，添加MIP-1α可抑制原始CD34+细胞（CD34+ CD45RAlow CD71low细胞）的数量扩增，而不抑制富含髓系（CD34+ CD45RA+ CD71low细胞）或红系（CD34+ CD45RAlow CD71+细胞）祖细胞的更成熟亚群的增殖。TGF-β显著降低了所有三个亚群的增殖，尽管其对红系谱系细胞的影响更为明显，尤其是未成熟的红系祖细胞。同样，TNF-α优先抑制富含红系细胞的亚群中的总核细胞和CD34+细胞生成。然而，与TGF-β不同，TNF-α优先抑制更成熟的红系祖细胞的增殖。在另一组实验中，将MIP-1α、TGF-β和TNF-α添加到从胎儿肝脏中纯化出的总CD34+细胞的培养物中。鉴于这些细胞中所含的大多数祖细胞是红系祖细胞，这三种细胞因子的抑制作用与在CD34+ CD45RAlow CD71+脐带血细胞培养中观察到的相似。本研究结果表明，MIP-1α、TGF-β和TNF-α有能力调节细胞因子诱导的脐带血和胎儿肝脏祖细胞的增殖。这三种细胞因子的不同作用证实了它们作为造血调节因子的多效性本质。
