Differentiation of epidermal Langerhans cells in macrophage colony-stimulating-factor-deficient mice homozygous for the osteopetrosis (op) mutation.

The osteopetrosis (op) mutation is within the gene for macrophage colony-stimulating factor (M-CSF). Homozygotes (op/op) lack M-CSF activity and show abnormalities in the differentiation of osteoclasts and other cells within the macrophage lineage. The effect of the op mutation on the development of Langerhans cells (LC) was determined in order to assess differentiation of such cells in vivo in the absence of M-CSF. (C57BL/6J X C3HeB/FeJ)F2-op/op and +/? Littermate control mice were raised from +/? breeders obtained from the Jackson Laboratory. The mice were killed with ether anesthesia at 4 weeks after birth and skin specimens were excised and examined by immunohistochemistry using anti-mouse pan macrophage monoclonal antibodies (MoAb), F4/80 and BM8; anti-mouse LC MoAb, NLDC-145, M1-8, and MIDC8; and anti-mouse Ia MoAb, M5/114. In epidermal sheets, numbers of LC were counted. Histochemical staining of adenosine diphosphatase (ADPase) localization was also performed as a marker of LC. Epidermal LC from op/op mice showed reactivity with all these MoAb. Numbers of LC were slightly reduced, but the reduction was not significant statistically. The presence of Birbeck granules in LC of op/op mice was confirmed by electron microscopy but the cytoplasmic projection of LC was not prominent. From these results, it appears obvious that the development and differentiation of LC do not require M-CSF.