Carlino J A, Higley H R, Creson J R, Avis P D, Ogawa Y, Ellingsworth L R
Department of Immunology, Celtrix Laboratories, Incorporated, Palo Alto, California 94303.
Exp Hematol. 1992 Sep;20(8):943-50.
Transforming growth factor beta 1 (TGF-beta 1) has been shown to inhibit the development of most early hemopoietic progenitors in vitro. The present series of in vivo experiments show that TGF-beta 1 can simultaneously augment and suppress distinct cell lineages in peripheral and central hemopoietic compartments. Mice treated daily for 7-14 days with s.c. injections of TGF-beta 1 exhibited up to a 95% reduction in circulating platelets and a 50% reduction in red cell counts, whereas a 50%-400% increase occurred in circulating white cells with the morphology of small lymphocytes. Decreased erythrocytes were also evident in the splenic red pulp and bone marrow sinusoids. A dramatic increase in granulopoiesis occurred in the spleen and bone marrow, followed by a peripheral neutrophilia 1 week after treatments ceased. All effects were completely reversible, with normal histologic and hematologic profiles evident 2 weeks after cessation of treatments. Thus, TGF-beta 1 can differentially regulate multiple hemopoietic pathways in a systemic, reversible, and dose-dependent fashion. These actions may be mediated by the direct effects of TGF-beta 1 or through modulation of secondary cytokines and receptors.
转化生长因子β1(TGF-β1)已被证明在体外可抑制大多数早期造血祖细胞的发育。本系列体内实验表明,TGF-β1可同时增强和抑制外周和中枢造血隔室中不同的细胞谱系。每天皮下注射TGF-β1 7至14天的小鼠,循环血小板减少高达95%,红细胞计数减少50%,而循环白细胞中具有小淋巴细胞形态的细胞增加了50%至400%。脾红髓和骨髓血窦中的红细胞也减少。脾脏和骨髓中粒细胞生成显著增加,治疗停止1周后外周血中性粒细胞增多。所有效应都是完全可逆的,治疗停止2周后组织学和血液学指标恢复正常。因此,TGF-β1可以以系统、可逆和剂量依赖的方式差异性调节多种造血途径。这些作用可能由TGF-β1的直接作用介导,或通过调节次级细胞因子和受体来实现。