HYPERGLYCEMIA AUGMENTS MACROPHAGE GROWTH-RESPONSES TO COLONY-STIMULATING FACTOR-I

Pathologic changes produced (or potentiated) by the diabetic state inc lude diabetic retinopathy, nephropathy, and atherosclerosis. There is evidence that the macrophage is implicated in the pathogenesis of thes e lesions. One of the growth factors known to exert a profound influen ce on macrophage physiology is colony-stimulating factor-1 (CSF-1). CS F-1 has previously been shown to be produced by endothelial cells, mes angial cells, and vascular smooth muscle cells, and it is reasonable t o suggest that the interaction of this factor on infiltrating macropha ges is an event that may have pivotal importance in the formation of d iabetic lesions. We report on the modulating influence of hyperglycemi a on the proliferative response of mouse splenic macrophages to CSF-1. Our studies showed that hyperglycemia enhanced the growth response of such macrophages to CSF-1. The mechanism underlying this enhanced res ponse was examined, and it was demonstrated that hyperglycemia induced a threefold increase in CSF-1 receptor (CSF-1r) mRNA expression as vi sualized by Northern blot analysis. These investigations provide insig ht into one of the molecular mechanisms potentially relevant to the ge nesis of diabetic lesions in the host. Copyright (C) 1996 by W.B. Saun ders Company