Taetle R, Guittard J P, Mendelsohn J M
Exp Hematol. 1980 Nov;8(10):1190-1201.
The effect of prostaglandin E1 (PGE1) on the in vitro proliferation of peripheral blood granulocyte/macrophage progenitors (CFUc) from the patients with chronic myeloproliferative disorders was examined. PGE1 was found to be a dose-dependent inhibitor of normal peripheral blood and bone marrow CFUc. Peripheral blood CFUc from patients with chronic myelogenous leukemia (CML) showed normal inhibition when cultured in the absence of exogenous colony stimulating factor (CSF). The addition of CSF to CML peripheral blood cultures resulted in complete abrogation of normal PGE1 inhibition. Dose-titration studies in which increasing amounts of CSF were added to CML cultures showed decreasing PGE1 inhibition with increasing CSF concentration. This observation indicated increased efficiency of competition between the colony stimulating effect of CSF and the colony inhibitory effect of PGE1 in CML. Peripheral blood CFUc from patients with myelofibrosis/myeloid metaplasia (MM) showed heterogeneous responses to PGE1 with complex dose-effect curves showing variable combinations of stimulation and inhibition of CFUc proliferation. Further studies showed that these effects of PGE1 were blocked by the prostaglandin antagonist SC-19220, and were not due to elaboration of CSF or non-CSF enhancers of CFUc proliferation from MM adherent cells. Cell fractionation studies in 2 patients, with MM showed dual populations of CFUc, one responding abnormally, and another normally to PGE1, accounting in part for the complex dose-response curves. These studies indicate that significant abnormalities exist in the in vitro response to PGE1 by CFUc from patients with chronic myeloproliferative disorders. Deficiencies in PGE 1 inhibition may contribute to the excess myelopoiesis seen in these disorders.
研究了前列腺素E1（PGE1）对慢性骨髓增殖性疾病患者外周血粒细胞/巨噬细胞祖细胞（CFUc）体外增殖的影响。发现PGE1是正常外周血和骨髓CFUc的剂量依赖性抑制剂。慢性粒细胞白血病（CML）患者的外周血CFUc在无外源性集落刺激因子（CSF）培养时表现出正常的抑制作用。向CML外周血培养物中添加CSF导致正常PGE1抑制作用完全消除。在CML培养物中添加越来越多CSF的剂量滴定研究表明，随着CSF浓度增加，PGE1抑制作用减弱。这一观察结果表明，在CML中，CSF的集落刺激作用与PGE1的集落抑制作用之间的竞争效率提高。骨髓纤维化/髓样化生（MM）患者的外周血CFUc对PGE1表现出异质性反应，复杂的剂量效应曲线显示CFUc增殖的刺激和抑制有不同组合。进一步研究表明，PGE1的这些作用被前列腺素拮抗剂SC-19220阻断，且不是由于MM贴壁细胞产生CSF或CFUc增殖的非CSF增强剂所致。对2例MM患者进行的细胞分级研究显示存在双群体CFUc，其中一群对PGE1反应异常，另一群反应正常，这部分解释了复杂的剂量反应曲线。这些研究表明，慢性骨髓增殖性疾病患者的CFUc对PGE1的体外反应存在明显异常。PGE1抑制作用的缺陷可能导致这些疾病中出现的髓系细胞过度增殖。
