Takahashi K, Naito M, Umeda S, Shultz L D
Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Am J Pathol. 1994 Jun;144(6):1381-92.
To elucidate the effects of macrophage colony-stimulating factor (M-CSF) on Kupffer cells and monocyte/macrophages in hepatic granuloma formation, we examined granulomas produced by glucan injection in the liver of osteopetrotic mice and littermates with or without M-CSF administration. In the osteopetrotic mice, monocytes were deficient in peripheral blood, and their number did not increase after glucan injection. Hepatic granulomas were formed in the osteopetrotic mice by glucan injection without a supply of blood monocytes. During this process, M-CSF-independent Kupffer cells proliferated, particularly before the granuloma formation, clustered in the hepatic sinusoid, and transformed into epithelioid cells and multinuclear giant cells. In the M-CSF-treated osteopetrotic mice, glucan injection induced an increase in the number of blood monocytes and formed hepatic granulomas at a nearly similar degree to that of littermate mice. Thus, it is concluded that neither monocytes nor M-CSF are necessary for granuloma formation. In contrast, Kupffer cells play a crucial role as granulomas develop in M-CSF-uninjected osteopetrotic mice.
为阐明巨噬细胞集落刺激因子（M-CSF）对肝肉芽肿形成过程中枯否细胞及单核细胞/巨噬细胞的影响，我们检测了给骨质石化小鼠及其同窝小鼠注射葡聚糖后，在给予或未给予M-CSF的情况下所产生的肉芽肿。在骨质石化小鼠中，外周血单核细胞缺乏，注射葡聚糖后其数量也不增加。在没有血液单核细胞供应的情况下，通过给骨质石化小鼠注射葡聚糖形成了肝肉芽肿。在此过程中，不依赖M-CSF的枯否细胞增殖，尤其是在肉芽肿形成之前，聚集在肝血窦中，并转化为上皮样细胞和多核巨细胞。在经M-CSF处理的骨质石化小鼠中，注射葡聚糖导致血液单核细胞数量增加，并形成了与同窝小鼠程度相近的肝肉芽肿。因此，可以得出结论，单核细胞和M-CSF对于肉芽肿形成均非必需。相反，在未注射M-CSF的骨质石化小鼠中，随着肉芽肿的发展，枯否细胞发挥了关键作用。
