Deutsch V R, Eldor A, Olson T, Barak V, Pick M, Nagler A
Department of Hematology, Hadassah University Hospital, Jerusalem, Israel.
Med Oncol. 1996 Mar;13(1):31-42. doi: 10.1007/BF02988839.
Plasma obtained from lethally irradiated animals contains a megakaryocyte (MK) growth factor which has recently been identified as the ligand for the c-mpl receptor and has been named thrombopoietin (TPO). We demonstrate that post-irradiation aplastic canine plasma (PICS-J) and plasma from a human subject (ML) who was accidentally exposed to lethal irradiation, contain high levels of this activity, which support both MK proliferation and maturation in a dose-dependent manner. These plasma were far more active in stimulating human MK colony formation than other types of thrombocytopenic plasma or a number of exogenously added human recombinant cytokines and their combinations. The addition of stem cell factor (SCF), which alone has a minimal stimulatory affect, to post lethal-irradiation plasma provided a synergistic stimulation of megakaryocytopoiesis both in colony assays and liquid cultures. In colony assays, the combination of SCF with PICS-J or ML almost doubled the number of burst forming units (BFU-MK) and provided a 1.5-fold increase in colony forming units (CFU-MK). A 1.6-fold increase in the number of CD34+ BM cell-derived MK colonies was also elicited. In liquid cultures, the presence of both SCF and PICS-J or ML induced the appearance of a high proportion of CD34+ (6.56% vs 0.6% control) and CD41+ (3.5% vs 1.2% control) cells after 3 days in culture. By day 10, 66.8 x 10(4) CD41+ cells and 29.8 x 10(4) CD34+ cells were derived from 2 x 10(6) BMMC originally seeded. We propose that these unique plasma, which do not contain elevated level of IL-6, IL-3, GM-CSF, IL-1 beta, erythropoietin or SCF, probably contain high levels of TPO. The addition of SCF to the post-irradiation plasma provides a synergistic stimulation of megakaryocytopoiesis which may become relevant for future clinical application.
从接受致死剂量照射的动物体内获取的血浆中含有一种巨核细胞（MK）生长因子，该因子最近被确定为c-mpl受体的配体，并被命名为血小板生成素（TPO）。我们证明，照射后再生障碍性犬血浆（PICS-J）以及一名意外遭受致死剂量照射的人类受试者（ML）的血浆中，含有高水平的这种活性物质，它们以剂量依赖的方式支持MK的增殖和成熟。这些血浆在刺激人MK集落形成方面比其他类型的血小板减少症血浆或多种外源性添加的人重组细胞因子及其组合更具活性。单独作用时对巨核细胞生成刺激作用极小的干细胞因子（SCF），添加到致死剂量照射后的血浆中，在集落测定和液体培养中对巨核细胞生成均产生协同刺激作用。在集落测定中，SCF与PICS-J或ML联合使用使爆式形成单位（BFU-MK）数量几乎增加了一倍，集落形成单位（CFU-MK）增加了1.5倍。CD34+骨髓细胞来源的MK集落数量也增加了1.6倍。在液体培养中，培养3天后，SCF与PICS-J或ML共同存在时诱导出现了高比例的CD34+细胞（6.56%对0.6%对照）和CD41+细胞（3.5%对1.2%对照）。到第10天，从最初接种的2×10⁶骨髓单个核细胞（BMMC）中产生了66.8×10⁴个CD41+细胞和29.8×10⁴个CD34+细胞。我们推测，这些独特的血浆中不含有升高水平的IL-6、IL-3、GM-CSF、IL-1β、促红细胞生成素或SCF，但可能含有高水平的TPO。向照射后血浆中添加SCF对巨核细胞生成产生协同刺激作用，这可能对未来的临床应用具有重要意义。
