DIABETIC RBC-INDUCED OXIDANT STRESS LEADS TO TRANSENDOTHELIAL MIGRATION OF MONOCYTE-LIKE HL-60 CELLS

Red blood cells (RBC) from patients with diabetes mellitus exhibit an increased propensity to adhere to cultured human umbilical vein endoth elial cells (HUVEC) as a result of interaction of advanced glycation e nd products with their counter receptors, contributing to the pathogen esis of vascular complications. We determined whether the interaction of diabetic RBC with HUVEC induced cellular oxidant stress that would culminate in adherence and diapedesis of monocytes, these being initia ting events in endothelial injury and atherogenesis. We show that the adherence of diabetic RBC (2% hematocrit), but not normal RBC, to HUVE C results in a fourfold increase in the production of lipid peroxides. Furthermore, diabetic RBC-induced oxidant stress causes a sixfold inc rease in platelet endothelial cell adhesion molecule-1 (PECAM-1) phosp horylation and doubles transendothelial migration of monocyte-like HL- 60 cells; both are blocked by antioxidants and protein kinase C (PKC) inhibitors. Our results show that the adherence of diabetic RBC to end othelial cells initiates a cascade of cellular events resulting in PKC activation, causing PECAM-1 phosphorylation and concomitant transendo thelial migration of monocytes. The increased diapedesis of monocytes, brought about by the interaction of diabetic RBC across vascular endo thelium, may play an important role in accelerated atherosclerosis and cardiovascular disease in diabetics.