Hyperglycemia augments macrophage growth responses to colony-stimulating factor-1.
Pathologic changes produced (or potentiated) by the diabetic state include diabetic retinopathy, nephropathy, and atherosclerosis. There is evidence that the macrophage is implicated in the pathogenesis of these lesions. One of the growth factors known to exert a profound influence on macrophage physiology is colony-stimulating factor-1 (CSF-1). CSF-1 has previously been shown to be produced by endothelial cells, mesangial cells, and vascular smooth muscle cells, and it is reasonable to suggest that the interaction of this factor on infiltrating macrophages is an event that may have pivotal importance in the formation of diabetic lesions. We report on the modulating influence of hyperglycemia 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 response was examined, and it was demonstrated that hyperglycemia induced a threefold increase in CSF-1 receptor (CSF-1r) mRNA expression as visualized by Northern blot analysis. These investigations provide insight into one of the molecular mechanisms potentially relevant to the genesis of diabetic lesions in the host.
Saini
A
A
Renal Section, Department of Medicine, Veterans Administration Medical Center, Washington 20422, DC, USA.
Liu
Y J
YJ
Cohen
D J
DJ
Ooi
B S
BS
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism
D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D016186:Receptor, Macrophage Colony-Stimulating Factor; D005947:Glucose