Op/op mice defective in production of functional colony-stimulating factor-1 lack macrophages in muscularis externa of the small intestine

The osteopetrotic (op/op) mutant mouse possesses an inactivating mutation i n the colony-stimulating factor-1 (CSF-1) gene, which results in the absenc e of certain macrophages and in osteopetrosis, following a lack of osteocla sts. Studies of the op/op mouse indicate that CSF-1-dependent tissue macrop hages 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 reg ularly distributed macrophages in the muscularis externa of the small intes tine and wanted to extend these studies to the op/op mouse. The present inv estigations 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 muscl e layers, with only an occasional macrophage present in the subserosa. In t he lamina propria and submucosa, macrophage numbers are reduced. In all oth er respects the muscularis externa appears normal, including normal organiz ation and number of interstitial cells of Cajal. Control and op/op mice bot h lack cells expressing CD3 (T lymphocytes), CD45R/B220 (B lymphocytes) and mast cells in the muscularis externa. This leaves the muscularis externa m acrophages as the most likely source of local cytokine production under suc h conditions as postoperative ileus and intussusception in infants, where t he muscularis externa appears to be one target of cytokines. We conclude th at the lack of macrophages, combined with the preservation of otherwise nor mal structure, will make the op/op mouse a valuable model by which to asses s the functions and relative importance of the muscularis externa macrophag es in relation to intestinal motility under normal and pathological conditi ons.