Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors
Human immunodeficiency virus infection of bone marrow endothelium reduces induction of stromal hematopoietic growth factors
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DOI：
10.1182/blood.v87.3.919.bloodjournal873919
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发表时间：
1996-02-01
期刊：
影响因子：
20.3
通讯作者：
Nelson, JA
中科院分区：
文献类型：
--
作者：
Moses, AV;Williams, S;Nelson, JA
大多数人类免疫缺陷病毒（HIV）血清阳性患者在疾病进展过程中会出现与造血功能障碍相关的骨髓异常。 HIV相关造血功能障碍的一个重要表现是骨髓抑制后，骨髓恢复受损，这一过程已知部分由基质细胞衍生的造血生长因子的产生介导。我们试图检验以下假设：骨髓基质细胞在体内被 HIV-1 感染，从而导致某些基质细胞衍生的造血生长因子的产生不足。在本报告中，我们证明，骨髓微血管内皮细胞（MVEC）是基质的关键成分，是从 11 名连续 HIV 血清阳性患者获得的骨髓基质培养物中被 HIV 感染的主要细胞（5% 至 20%），尽管富含 MVEC 的 HIV 感染基质培养物组成性表达正常水平的白细胞介素 (IL)-4、IL-6、粒细胞。在这些培养物中，(G)-集落刺激因子 (CSF)、粒细胞-巨噬细胞 (GM)-CSF、肿瘤坏死因子 (TNF)-α、转化生长因子 (TGF)-β 和 Steel 因子、IL-1 α 诱导的 IL-6 和 G-CSF 释放显着减少。这些观察结果表明，骨髓 MVEC 的 HIV 感染降低了造血基质响应调节信号的能力，这些调节信号通常在需求增加期间增加血细胞生成。 (C) 1996 年，美国血液学会。
The majority of human immunodeficiency virus (HIV)-seropositive patients develop bone marrow abnormalities associated with hematopoietic malfunction during the progression of disease. One important manifestation of HIV-associated hematopoietic dysfunction is that after myelosuppression, bone marrow recovery, a process known to be mediated in part by the production of stromal cell-derived hematopoietic growth factors, is impaired. We sought to test the hypothesis that bone marrow stromal cells are infected by HIV-1 in vivo and that production of certain stromal cell-derived hematopoietic growth factors is deficient as a consequence. In this report, we demonstrate that bone marrow microvascular endothelial cells (MVEC), a key element of the stroma, are the predominant cells infected by HIV (5% to 20%) in bone marrow stromal cultures obtained from 11 consecutive HIV-seropositive patients, Although HIV-infected stromal cultures enriched for MVEC constitutively express normal levels of interleukin (IL)-4, IL-6, granulocyte (G)-colony-stimulating factor (CSF), granulocyte-macrophage (GM)-CSF, tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, and Steel factor, IL-1 alpha-induced release of IL-6 and G-CSF is significantly reduced in these cultures. These observations suggest that HIV infection of bone marrow MVEC reduces the capacity of hematopoietic stroma to respond to regulatory signals that normally augment blood cell production during periods of increased demand. (C) 1996 by The American Society of Hematology.