Regulation of hematopoietic stem cell activity by inflammation.
Regulation of hematopoietic stem cell activity by inflammation.
复制标题
DOI：
10.3389/fimmu.2013.00204
复制
发表时间：
2013
影响因子：
7.3
通讯作者：
Link DC
中科院分区：
文献类型：
--
作者：
Schuettpelz LG;Link DC
造血干细胞(HSCs)是一种静止细胞，具有自我更新能力和生成全部成熟血细胞的能力。造血干细胞通常驻留在骨髓中的特殊位置，帮助维持其静止和长期的再繁殖活动。越来越多的证据表明，炎症过程中诱导的某些细胞因子对骨髓中的HSCs有显著影响。I型和II型干扰素、肿瘤坏死因子和脂多糖(LPS)直接刺激HSC的增殖和分化，从而增加成熟效应白细胞的短期产量。然而，慢性炎性细胞因子信号可导致HSC耗竭，并可能促进血液系统恶性肿瘤的发展。促炎细胞因子，如G-CSF，也可以通过改变骨髓微环境，扰乱干细胞生态位，导致HSC动员进入血液，间接影响HSC。在这里，我们回顾了我们目前对炎症介质对造血干细胞影响的理解，并讨论了这些发现在骨髓衰竭和白血病发生方面的潜在临床意义。
Hematopoietic stem cells (HSCs) are quiescent cells with self-renewal capacity and the ability to generate all mature blood cells. HSCs normally reside in specialized niches in the bone marrow that help maintain their quiescence and long-term repopulating activity. There is emerging evidence that certain cytokines induced during inflammation have significant effects on HSCs in the bone marrow. Type I and II interferons, tumor necrosis factor, and lipopolysaccharide (LPS) directly stimulate HSC proliferation and differentiation, thereby increasing the short-term output of mature effector leukocytes. However, chronic inflammatory cytokine signaling can lead to HSC exhaustion and may contribute the development of hematopoietic malignancies. Pro-inflammatory cytokines such as G-CSF can also indirectly affect HSCs by altering the bone marrow microenvironment, disrupting the stem cell niche, and leading to HSC mobilization into the blood. Herein, we review our current understanding of the effects of inflammatory mediators on HSCs, and we discuss the potential clinical implications of these findings with respect to bone marrow failure and leukemogenesis.