Wiktor-Jedrzejczak W, Urbanowska E, Aukerman S L, Pollard J W, Stanley E R, Ralph P, Ansari A A, Sell K W, Szperl M
Department of Immunology, Military School of Medicine, Warsaw, Poland.
Exp Hematol. 1991 Nov;19(10):1049-54.
Mice that are mutant at the op locus have a severe deficiency of mononuclear phagocytes due to an inactivating mutation in the CSF-1 (macrophage colony-stimulating factor, M-CSF) gene. op/op mice are toothless, possessing skeletal abnormalities, a low body weight, and compromised fertility; they are osteopetrotic due to a deficiency of osteoclasts. The congenital osteopetrosis, toothless phenotype, osteoclast deficit, and the defects in splenic and femoral macrophages were corrected by routes of administration of human recombinant CSF-1 that maintained normal circulating CSF-1 concentrations. Early restoration of circulating CSF-1 was required for rescue of the toothless phenotype, but only partially restored body weight. In contrast, the deficiencies of pleural and peritoneal cavity macrophages and the reduced female fertility were not corrected by restoration of circulating CSF-1. These results suggest that although circulating CSF-1 is required for osteoclast and macrophage production, local synthesis and action of the growth factor are important for certain target cell populations.
由于集落刺激因子-1（巨噬细胞集落刺激因子，M-CSF）基因的失活突变，op位点突变的小鼠单核吞噬细胞严重缺乏。op/op小鼠无牙，存在骨骼异常、体重低和生育能力受损的问题；由于破骨细胞缺乏，它们患有骨质石化症。通过维持正常循环CSF-1浓度的人重组CSF-1给药途径，可纠正先天性骨质石化症、无牙表型、破骨细胞缺陷以及脾脏和股骨巨噬细胞的缺陷。循环CSF-1的早期恢复是挽救无牙表型所必需的，但只能部分恢复体重。相比之下，循环CSF-1的恢复并不能纠正胸膜和腹膜腔巨噬细胞的缺乏以及雌性生育能力的降低。这些结果表明，虽然破骨细胞和巨噬细胞的产生需要循环CSF-1，但生长因子的局部合成和作用对某些靶细胞群体很重要。
