Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse.
Role of colony stimulating factor-1 in the establishment and regulation of tissue macrophages during postnatal development of the mouse.
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发表时间：
1994-06
期刊：
影响因子：
4.6
通讯作者：
M. Cecchini;M. Dominguez;S. Mocci;A. Wetterwald;R. Felix;H. Fleisch;O. Chisholm;W. Hofstetter;J. Pollard;E. Stanley
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作者：
M. Cecchini;M. Dominguez;S. Mocci;A. Wetterwald;R. Felix;H. Fleisch;O. Chisholm;W. Hofstetter;J. Pollard;E. Stanley
集落刺激因子-1(CSF-1)调节单核巨噬细胞的存活、增殖和分化。骨质疏松(OP/OP)突变小鼠由于CSF-1基因的失活突变而缺乏CSF-1，并且缺乏几个单核吞噬细胞亚群。为了更全面地分析单核巨噬细胞建立和维持过程中对CSF-1的需求，本研究对OP/OP小鼠及其正常(+/OP或+/+)胎鼠巨噬细胞标志物F4/80和MOMA-1细胞在出生后3个月内的发育进行了研究。在正常小鼠中，组织F4/80+细胞的最大表达通常与器官发生最多和/或细胞周转的时间有关。根据组织的不同，F4/80+细胞密度随年龄增加或减少、或一过性增加或逐渐增加。在OP/OP小鼠中，正常含有F4/80+细胞的组织可分为F4/80+细胞缺失和F4/80+细胞密度降低、正常或最初正常然后降低的组织。为了解正常小鼠外周血中哪些F4/80+细胞受外周血脑脊液-1的调节，对3d起每天皮下注射重组人脑脊液-1的OP/OP小鼠外周血中外周血细胞因子浓度恢复到正常水平。这些研究表明，循环中的CSF-1对肝、脾和肾中的F4/80+细胞和脾中的MOMA-1+嗜金属巨噬细胞均有专一性调节。真皮、膀胱、骨髓和唾液腺的巨噬细胞以及肠道中的一个亚群可被循环的CSF-1部分恢复，而肌肉、肌腱、骨膜、滑膜、肾上腺的巨噬细胞和与消化道上皮密切相关的巨噬细胞不能通过循环的CSF-1的恢复而得到纠正，这表明它们只受这种生长因子的局部调节。OP/OP小鼠胸腺和淋巴结的朗格汉斯细胞、骨髓单核细胞和巨噬细胞未受循环CSF-1的明显影响，也未见明显减少，这与其他生长因子的调节一致。这些结果表明，单核巨噬细胞在对CSF-1的依赖性和向其呈递CSF-1的方式方面存在重要差异。他们还表明，CSF-1的普遍作用是通过刺激具有局部营养和/或清道夫(生理)功能的组织巨噬细胞的产生来影响器官发生和组织周转。参与炎症和免疫(病理)反应的巨噬细胞的个体发生和功能似乎依赖于其他因素。
Colony stimulating factor-1 (CSF-1) regulates the survival, proliferation and differentiation of mononuclear phagocytes. The osteopetrotic (op/op) mutant mouse is devoid of CSF-1 due to an inactivating mutation in the CSF-1 gene and is deficient in several mononuclear phagocyte subpopulations. To analyze more fully the requirement for CSF-1 in the establishment and maintenance of mononuclear phagocytes, the postnatal development of cells bearing the macrophage marker antigens F4/80 and MOMA-1, in op/op mice and their normal (+/op or +/+) littermates, were studied during the first three months of life. In normal mice, maximum expression of tissue F4/80+ cells was generally correlated with the period of maximum organogenesis and/or cell turnover. Depending on the tissue, the F4/80+ cell density either decreased, transiently increased or gradually increased with age. In op/op mice, tissues that normally contain F4/80+ cells could be classified into those in which F4/80+ cells were absent and those in which the F4/80+ cell densities were either reduced, normal or initially normal then subsequently reduced. To assess which F4/80+ populations were regulated by circulating CSF-1 in normal mice, op/op mice in which the circulating CSF-1 concentration was restored to above normal levels by daily subcutaneous injection of human recombinant CSF-1 from day 3 were analyzed. These studies suggest that circulating CSF-1 exclusively regulates both the F4/80+ cells in the liver, spleen and kidney and the MOMA-1+ metallophilic macrophages in the spleen. Macrophages of the dermis, bladder, bone marrow and salivary gland, together with a subpopulation in the gut, were partially restored by circulating CSF-1, whereas macrophages of the muscle, tendon, periosteum, synovial membrane, adrenals and the macrophages intimately associated with the epithelia of the digestive tract, were not corrected by restoration of circulating CSF-1, suggesting that they are exclusively locally regulated by this growth factor. Langerhans cells, bone marrow monocytes and macrophages of the thymus and lymph nodes were not significantly affected by circulating CSF-1 nor decreased in op/op mice, consistent with their regulation by other growth factors. These results indicate that important differences exist among mononuclear phagocytes in their dependency on CSF-1 and the way in which CSF-1 is presented to them. They also suggest that the prevalent role of CSF-1 is to influence organogenesis and tissue turnover by stimulating the production of tissue macrophages with local trophic and/or scavenger (physiological) functions. Macrophages involved in inflammatory and immune (pathological) responses appear to be dependent on other factors for their ontogenesis and function.(ABSTRACT TRUNCATED AT 400 WORDS)