Mikkelsen H B, Thuneberg L
Department of Medical Anatomy, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Cell Tissue Res. 1999 Mar;295(3):485-93. doi: 10.1007/s004410051254.
The osteopetrotic (op/op) mutant mouse possesses an inactivating mutation in the colony-stimulating factor-1 (CSF-1) gene, which results in the absence of certain macrophages and in osteopetrosis, following a lack of osteoclasts. Studies of the op/op mouse indicate that CSF-1-dependent tissue macrophages may belong to a trophic and/or scavenger subpopulation, which through their effect on other cell types can significantly affect tissue functions, and that cells which are CSF-1 independent have antigen presentation and immunological functions. We have previously identified a cell system of regularly distributed macrophages in the muscularis externa of the small intestine and wanted to extend these studies to the op/op mouse. The present investigations with light- and electron-microscopic methods using fluorescent dextran, methylene blue and immunohistochemistry (F4/80, anti-kit receptor, anti-CD3, anti-CD45R/B220) show that macrophages are absent from the muscle layers, with only an occasional macrophage present in the subserosa. In the lamina propria and submucosa, macrophage numbers are reduced. In all other respects the muscularis externa appears normal, including normal organization and number of interstitial cells of Cajal. Control and op/op mice both lack cells expressing CD3 (T lymphocytes), CD45R/B220 (B lymphocytes) and mast cells in the muscularis externa. This leaves the muscularis externa macrophages as the most likely source of local cytokine production under such conditions as postoperative ileus and intussusception in infants, where the muscularis externa appears to be one target of cytokines. We conclude that the lack of macrophages, combined with the preservation of otherwise normal structure, will make the op/op mouse a valuable model by which to assess the functions and relative importance of the muscularis externa macrophages in relation to intestinal motility under normal and pathological conditions.
骨石化（op/op）突变小鼠的集落刺激因子-1（CSF-1）基因存在失活突变，由于缺乏破骨细胞，导致某些巨噬细胞缺失并引发骨石化。对op/op小鼠的研究表明，依赖CSF-1的组织巨噬细胞可能属于营养性和/或清道夫亚群，它们通过对其他细胞类型的作用可显著影响组织功能，而不依赖CSF-1的细胞具有抗原呈递和免疫功能。我们之前在小肠肌层中鉴定出了一个规则分布的巨噬细胞系统，并希望将这些研究扩展到op/op小鼠。目前使用荧光葡聚糖、亚甲蓝和免疫组织化学（F4/80、抗kit受体、抗CD3、抗CD45R/B220）的光镜和电镜方法研究表明，肌层中没有巨噬细胞，仅在浆膜下层偶尔有一个巨噬细胞。在固有层和黏膜下层，巨噬细胞数量减少。在所有其他方面，肌层外观正常，包括Cajal间质细胞的正常组织和数量。对照小鼠和op/op小鼠的肌层中均缺乏表达CD3（T淋巴细胞）、CD45R/B220（B淋巴细胞）的细胞和肥大细胞。这使得肌层巨噬细胞成为婴儿术后肠梗阻和肠套叠等情况下局部细胞因子产生的最可能来源，在这些情况下肌层似乎是细胞因子的一个作用靶点。我们得出结论，巨噬细胞的缺失，加上其他结构保持正常，将使op/op小鼠成为一个有价值的模型，通过它可以评估正常和病理条件下肌层巨噬细胞与肠道运动相关的功能及相对重要性。
