Bernad A, Kopf M, Kulbacki R, Weich N, Koehler G, Gutierrez-Ramos J C
Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.
Immunity. 1994 Dec;1(9):725-31. doi: 10.1016/s1074-7613(94)80014-6.
The development of blood cells from hematopoietic stem cells is controlled by multiple cytokines. These growth factors influence survival, cell cycle status, differentiation into lineage-committed progenitors, final maturation into blood cells, and perhaps self-renewal of stem cells. The specific contribution of IL-6 to these processes in vivo was evaluated in mice with a targeted disruption of the IL-6 gene. Decreases in the absolute numbers of CFU-Sd12 and preCFU-S, as well as in the functionality of LTRSC in these mutant mice, suggests a role for IL-6 in the survival, self-renewal, or both of hematopoietic stem cells and early progenitors. In addition, as a result of the IL-6 deficiency, the control between proliferation and differentiation of the progenitor cells of the granulocytic-monocytic, megakaryocytic, and erythroid lineages into mature blood cells is altered, leading to abnormal levels of committed progenitors of these lineages and to a slow recovery from hematopoietic ablation.
造血干细胞向血细胞的发育受多种细胞因子控制。这些生长因子影响细胞存活、细胞周期状态、分化为定向祖细胞、最终成熟为血细胞,或许还影响干细胞的自我更新。通过对IL-6基因进行靶向破坏的小鼠,评估了IL-6在体内对这些过程的具体作用。这些突变小鼠中CFU-Sd12和preCFU-S的绝对数量以及长期再增殖造血干细胞(LTRSC)功能的降低,表明IL-6在造血干细胞和早期祖细胞的存活、自我更新或两者中发挥作用。此外,由于IL-6缺乏,粒细胞-单核细胞、巨核细胞和红系谱系的祖细胞向成熟血细胞增殖与分化之间的控制发生改变,导致这些谱系定向祖细胞水平异常,并使造血细胞消融后的恢复缓慢。