Proliferation, macrophage colony-stimulating factor, and macrophage colony-stimulating factor-receptor expression of alveolar macrophages in active sarcoidosis.

Alveolar macrophages (AM) in sarcoidosis display an enhanced mitotic activity. Immunocytochemical detection of the proliferation-associated Ki-67 antigen revealed significant increase in the number of proliferating AM in active sarcoidosis as compared with inactive stages of disease. Macrophage proliferation may provide an additional marker of disease activity. Since growth of macrophages is regulated by hematopoietic growth factors, we examined the expression of macrophage colony-stimulating factor (M-CSF), granulocyte M-CSF, and interleukin-3 by bronchoalveolar lavage cells in active sarcoidosis. Expression of granulocyte M-CSF or interleukin-3 genes could not be detected. AM in active sarcoidosis displayed M-CSF RNA to a comparable level like normal AM. They differed, however, in about 50% of cases analyzed, from normal AM by an enhanced level of c-fms proto-oncogene (M-CSF-receptor) expression. The enlarged proportion of proliferating AM in active sarcoidosis may be the result of an increased influx of strongly fms expressing macrophage precursors into the alveoli and autostimulation of macrophages by M-CSF.