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白细胞介素-1α和-1β对响应造血集落刺激因子的人骨髓细胞存活的影响。

Influence of IL-1 alpha and -1 beta on the survival of human bone marrow cells responding to hematopoietic colony-stimulating factors.

作者信息

Hangoc G, Williams D E, Falkenburg J H, Broxmeyer H E

机构信息

Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.

出版信息

J Immunol. 1989 Jun 15;142(12):4329-34.

PMID:2656864
Abstract

Purified recombinant human (rhu) IL-1 alpha and IL-1 beta were evaluated for their effects on the proliferation and survival of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells from normal human bone marrow (BM). Using nonadherent low density T lymphocyte depleted (NALT-) BM cells cultured in the presence or absence of IL-1, CSF-deprivation studies demonstrated that IL-1 alpha or IL-1 beta by itself did not enhance the proliferation of CFU-GM or BFU-E. They did, however, promote the survival of progenitors responding to the delayed addition of media conditioned by the 5637 cell line (5637 conditioned medium), rhu GM-CSF and erythropoietin. The survival promoting effects of IL-1 alpha on CFU-GM and BFU-E were neutralized by anti-IL-1 alpha mAb added to the cultures. The survival promoting effect of IL-1 alpha did not appear to be mediated by CSF, because neither CSF nor erythroid burst promoting activity were detectable in cultures in which NALT- cells were incubated with rhuIL-1 alpha. In addition, suboptimal concentrations of rhu macrophage CSF (CSF-1), G-CSF, GM-CSF, and IL-3, which were just below the levels that would stimulate colony formation, did not enhance progenitor cell survival. Survival of CFU-GM and BFU-E in low density (LD) bone marrow cells did not decrease as drastically as that in NALT- BM cells, and exogenously added IL-1 did not enhance progenitor cell survival of CFU-GM and BFU-E in LD BM cells. However, addition of anti-IL-1 beta decreased survival of CFU-GM and BFU-E in LD BM cells. These results implicate IL-1 in the prolonged survival of human CFU-GM and BFU-E.

摘要

对纯化的重组人(rhu)白细胞介素-1α(IL-1α)和白细胞介素-1β(IL-1β),评估了它们对来自正常人骨髓(BM)的粒细胞-巨噬细胞(CFU-GM)和红系(BFU-E)祖细胞增殖和存活的影响。使用在有或无IL-1的情况下培养的非贴壁低密度T淋巴细胞清除(NALT-)骨髓细胞,集落刺激因子剥夺研究表明,单独的IL-1α或IL-1β不会增强CFU-GM或BFU-E的增殖。然而,它们确实促进了祖细胞对5637细胞系条件培养基(5637条件培养基)、rhu粒细胞-巨噬细胞集落刺激因子(GM-CSF)和促红细胞生成素延迟添加的反应存活。添加到培养物中的抗IL-1α单克隆抗体可中和IL-1α对CFU-GM和BFU-E的存活促进作用。IL-1α的存活促进作用似乎不是由集落刺激因子介导的,因为在NALT-细胞与rhuIL-1α孵育的培养物中未检测到集落刺激因子或红系爆式促进活性。此外,低于刺激集落形成水平的次优浓度的rhu巨噬细胞集落刺激因子(CSF-1)、粒细胞集落刺激因子(G-CSF)、GM-CSF和白细胞介素-3不会增强祖细胞存活。低密度(LD)骨髓细胞中CFU-GM和BFU-E的存活不像NALT-骨髓细胞中那样急剧下降,并且外源添加的IL-1不会增强LD骨髓细胞中CFU-GM和BFU-E的祖细胞存活。然而,添加抗IL-1β会降低LD骨髓细胞中CFU-GM和BFU-E的存活。这些结果表明IL-1参与了人CFU-GM和BFU-E的延长存活。

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