Wiktor-Jedrzejczak W, Ratajczak M Z, Ptasznik A, Sell K W, Ahmed-Ansari A, Ostertag W
Department of Immunology, Military School of Medicine, Warsaw, Poland.
Exp Hematol. 1992 Sep;20(8):1004-10.
Osteopetrosis and the absence of colony-stimulating factor 1 (CSF-1) in op/op mice are associated with decreased cellularity of the bone marrow (to one tenth of the normal), a very significant reduction in the number of cells recovered from peritoneal, pleural, and alveolar lavages, moderate leukopenia, and a slight decrease in the number of cells per spleen and thymus. Furthermore, op/op mice possess deficiencies in the number of macrophages in various organs. These cells are apparently absent in the bone marrow, severely reduced (5%-15% of the normal number) in peritoneal and pleural cavities and in the lungs. In addition, a marked decrease in the frequency and total number of circulating monocytes is present (5% of the normal). The deficiency of macrophages is less severe in the liver, spleen, and thymus of op/op mice (approximately 30% of those seen in normal). There is a concomitant redistribution of macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) in op/op mice from the marrow to the spleen and liver, associated with an increased sensitivity to interleukin 3 (IL-3). Their total number is decreased at least threefold compared to control mice. Moreover, op/op mice have at least a fivefold reduction in the total number of day-11 spleen colony-forming units (CFU-S) associated with their redistribution to the spleen and liver. These data suggest that the macrophage system in op/op mice is reduced at all levels tested, that is, at the level of mature macrophages, the level of progenitors, and the level of stem cells, whereas the redistribution of progenitor and stem cells could be viewed as a secondary consequence of osteopetrosis. Furthermore, these data suggest that macrophage dependency in vivo on CSF-1 is limited and different in various organs. Particularly in the liver, spleen, and thymus, other growth factors may significantly compensate for CSF-1 deficiency. Based on the relative decrease in the number of CFU-GM in the op/op mice, it appears that the population size of these progenitors is less dependent on CSF-1 than the hematopoietic stem cell population size as evidenced by the day-11 CFU-S assay. The day-11 CFU-S population is severely reduced in op/op mice, suggesting a physiological involvement of CSF-1 in expanding its size. These data provide evidence that CSF-1, besides acting on the final and intermediate stages of macrophage maturation, may also play a role in early stages of hematopoiesis.
骨硬化症与op/op小鼠中集落刺激因子1（CSF-1）的缺失有关，表现为骨髓细胞数量减少（降至正常的十分之一），从腹膜、胸膜和肺泡灌洗中回收的细胞数量显著减少，中度白细胞减少，脾脏和胸腺中细胞数量略有下降。此外，op/op小鼠各器官中的巨噬细胞数量存在缺陷。骨髓中明显缺乏这些细胞，腹膜腔、胸膜腔和肺中的数量严重减少（为正常数量的5%-15%）。此外，循环单核细胞的频率和总数显著下降（为正常的5%）。op/op小鼠肝脏、脾脏和胸腺中的巨噬细胞缺陷不太严重（约为正常的30%）。op/op小鼠中巨噬细胞祖细胞（粒细胞-巨噬细胞集落形成单位，CFU-GM）从骨髓向脾脏和肝脏发生了重新分布，且对白细胞介素3（IL-3）的敏感性增加。与对照小鼠相比，其总数至少减少了三倍。此外，op/op小鼠第11天脾脏集落形成单位（CFU-S）的总数至少减少了五倍，且其向脾脏和肝脏发生了重新分布。这些数据表明，op/op小鼠的巨噬细胞系统在所有测试水平上均减少，即在成熟巨噬细胞水平、祖细胞水平和干细胞水平，而祖细胞和干细胞的重新分布可视为骨硬化症的继发后果。此外，这些数据表明，体内巨噬细胞对CSF-1的依赖性有限且在各器官中有所不同。特别是在肝脏、脾脏和胸腺中，其他生长因子可能显著补偿CSF-1的缺乏。基于op/op小鼠中CFU-GM数量的相对减少，似乎这些祖细胞的群体大小对CSF-1的依赖性低于造血干细胞群体大小，这在第11天CFU-S测定中得到了证实。op/op小鼠中第11天CFU-S群体严重减少，表明CSF-1在扩大其大小方面有生理作用。这些数据提供了证据，表明CSF-1除了作用于巨噬细胞成熟的终末和中间阶段外，还可能在造血的早期阶段发挥作用。
