GM-CSF AND M-CSF EXPRESSION IS ASSOCIATED WITH MACROPHAGE PROLIFERATION IN PROGRESSING AND REGRESSING RABBIT ATHEROMATOUS LESIONS

Recent studies have documented that macrophages are a significant cell component of atherosclerotic lesions and may play a significant role in the pathogenesis of these lesions. It has also been documented that markers of cell proliferation (e.g., the proliferating cell nuclear antigen) can be expressed by macrophage subpopulations in atherosclerotic lesions, and there is great interest in identifying cell mediated factors which might be instrumental in macrophage proliferation in this context, perhaps accounting for the persistence of macrophages within this context. Important candidates for this function include granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); the latter has been previously demonstrated to be expressed in human and rabbit atherosclerotic lesions. We have extended these studies by studying immunocytochemical localization of GM-CSF and M-CSF in progressing and regressing lesions of cholesterol-fed rabbits, documenting expression of these factors predominantly in macrophages, but also in some smooth muscle-cells and endothelial cells. The simultaneous documentation of macrophage subpopulations expressing the proliferating cell nuclear antigen in the same lesions provides evidence to support the hypothesis that macrophage GM-CSF and M-CSF production represents a factor underlying macrophage proliferation and accumulation in atherosclerotic lesions. (C) 1994 Academic Press. Inc.