Khoury E, Lemoine F M, Baillou C, Kobari L, Deloux J, Guigon M, Najman A
Department of Hematology, Faculté de médecine, Saint Antoine, Paris, France.
Exp Hematol. 1992 Sep;20(8):991-7.
Although tumor necrosis factor alpha (TNF alpha) exerts a variety of activities on hematopoietic cells, suggesting it may have some potential therapeutic applications, its long-term effects on hematopoiesis are not well defined. Therefore, we took the advantage of long-term bone marrow cultures (LTBMCs) to evaluate the long-term role of TNF alpha on both the microenvironment and the hematopoietic progenitors. LTBMCs were inoculated with 100 U/ml of recombinant human TNF alpha (rhTNF alpha) either at the onset of the cultures (d0) or at day 21 (d21) when the adherent layer (AL) was already established. Then TNF alpha was added at each weekly medium change. The cellularity and the content of progenitors in both the nonadherent layer (NAL) and AL, the formation of the AL, and the presence of various cytokines in the supernatants were examined weekly. The data showed 1) a strong and durable inhibitory effect on total nonadherent cells; 2) a rapid and transient inhibition of NA progenitors, whereas adherent progenitors were lately affected; and 3) microenvironmental changes consisting of the disappearance of adipocytes and the secretion of high levels of interleukin 6. The results suggest that the inhibitory effects of TNF alpha on the NAL are in part counterbalanced by stromal modifications that in turn lead to a faster exhaustion of hematopoiesis.
尽管肿瘤坏死因子α（TNFα）对造血细胞具有多种作用，提示其可能具有一些潜在的治疗应用，但它对造血功能的长期影响尚不明确。因此，我们利用长期骨髓培养（LTBMCs）来评估TNFα对微环境和造血祖细胞的长期作用。在培养开始时（第0天）或在第21天（d21）当贴壁层（AL）已经形成时，将100 U/ml的重组人TNFα（rhTNFα）接种到LTBMCs中。然后在每次更换培养基时添加TNFα。每周检查非贴壁层（NAL）和AL中的细胞数量和祖细胞含量、AL的形成以及上清液中各种细胞因子的存在情况。数据显示：1）对总非贴壁细胞有强烈且持久的抑制作用；2）对NA祖细胞有快速且短暂的抑制作用，而贴壁祖细胞较晚受到影响；3）微环境变化包括脂肪细胞的消失和高水平白细胞介素6的分泌。结果表明，TNFα对NAL的抑制作用部分被基质改变所抵消，而基质改变反过来又导致造血功能更快耗尽。
