Mice with a regenerative wound healing capacity and an SLE autoimmune phenotype contain elevated numbers of circulating and marrow-derived macrophage progenitor cells
Mice with a regenerative wound healing capacity and an SLE autoimmune phenotype contain elevated numbers of circulating and marrow-derived macrophage progenitor cells
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DOI：
10.1016/j.bcmd.2004.10.001
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发表时间：
2005-01-01
影响因子：
2.3
通讯作者：
Lennon, G
中科院分区：
文献类型：
--
作者：
Davis, TA;Lennon, G
来自MRL菌株的小鼠容易发生系统性红斑狼疮（SLE），并表现出加速的伤口愈合和无疤痕组织再生；然而，涉及这些临床相关病理的许多机制尚不清楚。先前的研究描述了巨噬细胞积聚和狼疮易感小鼠的功能缺陷。单核巨噬细胞也被证明具有高度的可塑性。为了确定MRL小鼠的造血系统是否存在先天差异，我们评估了多种组织中的造血祖细胞含量以及衍生骨髓和巯基糖酸盐（TG）诱导的腹膜巨噬细胞的增殖反应。我们的实验表明，MRL小鼠的循环血液白细胞和血小板数量明显减少。更引人注目的是，我们发现MRL血液和骨髓中含有异常大量独特且可检测的巨噬细胞集落刺激因子应答细胞，这些细胞具有巨噬细胞集落形成细胞前体的特征。在培养中，与来自对照C57BL/6小鼠的细胞相比，来自MRL小鼠的这种细胞类型和巯基乙酸盐诱导的腹腔巨噬细胞可以通过巨噬细胞集落刺激因子广泛扩增，获得原位的“f-mac样”(见Y Zhao， D. Glesne和E. Huberman， A人外周血单核细胞衍生的亚群作为多能干细胞。Proc。国家的。学会科学。（美国）100,(2003)2426-2431.)电镀在塑料表面时的形貌。我们的研究结果表明，这些巨噬细胞祖细胞数量的增加及其潜在的分化可塑性可能在系统性红斑狼疮的发病中发挥功能作用，也可能有助于在MRL小鼠中观察到的加速和无疤痕的组织再生修复反应。(C) 2004爱思唯尔公司版权所有。
Mice from the MRL strain are prone to develop systemic lupus erythematosus (SLE) and have demonstrated accelerated wound healing and scarless tissue regeneration; however, many of the mechanisms involved in these clinically relevant pathologies are unclear. Prior studies have described macrophage accumulation and functional defects in mice prone to lupus. Monocyte-macrophages have also been shown to have a high degree of plasticity. To determine whether there might be innate differences in the hematopoietic systems of MRL mice, we evaluated hematopoietic progenitor cell content in a variety of tissues and the proliferative responses of derived marrow and thioglycolate (TG)-elicited peritoneal macrophages. Our experiments reveal that MRL mice have significantly lower numbers of circulating blood leukocytes and platelets. Even more strikingly, we found that MRL blood and marrow contain an unusually robust number of unique and assayable macrophage colony-stimulating factor responsive cells which have the characteristics of macrophage colony-forming cell precursors. In culture, in contrast to cells derived from control C57BL/6 mice, this cell type and thioglycolate-elicited peritoneal macrophages from MRL mice can be extensively expanded with just macrophage colony-stimulating factor to acquire an in situ "f-mac-like" (see Y Zhao, D. Glesne and E. Huberman, A human peripheral blood monocyte-derived subset acts as pluripotent stem cells. Proc. Natl. Acad. Sci. U.S.A. 100, (2003) 2426-2431.) morphology when plated on plastic surfaces. Our results suggest that these increased numbers of macrophage progenitor cells and their potential differentiation plasticity may play a functional role in the onset of systemic lupus erythematosus and may also contribute to the accelerated and scarless tissue regenerative repair response observed in MRL mice. (C) 2004 Elsevier Inc. All rights reserved.