期刊
EXPERIMENTAL HEMATOLOGY
卷 34, 期 11, 页码 1451-1461出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.exphem.2006.06.014
关键词
-
Objective. Cytokines released during inflammatory processes have been proposed to play a central role in mediating mechanism(s) leading to anemia. Here, we used CpG-ODN to investigate the effects of a pro-inflammatory response on the pathophysiological processes leading to anemia. Methods. Naive and erythropoietin (EPO)-treated mice were injected for 2 days with 100 Pg CpG-ODN or control ODN and the effects on the course of red blood cell (RBC) and reticulocyte counts, RBC turnover, and EPO-stimulated maturation of erythroid cells were analyzed. To study the effect of CpG-ODN on erythroid cell maturation in vitro, we obtained primary EPO-responsive cells by treating mice with thiamphenicol (15 mg/g body weight). Results. CpG-ODN-treated mice developed anemia, which persisted for 5 days and was associated with a 50% reduction in EPO-stimulated differentiation of EPOR+ cells to TER119(+) erythroblasts. CpG-ODN-induced suppression required accessory cells, including antigen presenting cells, which activated other cells to produce pro-inflammatory cytokines. In vitro neutralization of IFN-gamma, but not IL-12, TNF-alpha, IFN-alpha, IL-1 alpha, or IL-1 beta, abrogated the erythropoietic suppression induced by CpG-ODN. The anemia observed in CpG-ODN-treated mice was also associated with reduced RBC survival in vivo, as demonstrated by a sevenfold to eightfold higher turnover of biotinylated RBC compared to control ODN-treated mice. In vivo IFN-gamma neutralization confirmed that IFN-gamma contributed to erythropoietic suppression but not reduced RBC survival. Conclusions. Together, these results demonstrate that CpG-ODN anemia is associated with suppressed erythropoiesis and decreased RBC survival. Importantly, CpG-ODN-induced IFN-gamma was found to be the major factor mediating erythropoietic suppression but not decreased RBC survival. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据