Glucose-induced transmigration of monocytes is linked to phosphorylation of PECAM-1 in cultured endothelial cells.
The adherence of circulating monocytes to the endothelium, their migration into the subendothelium, and the subsequent formation of foam cells are initial events in the pathogenesis of atherosclerosis. However, the effect of hyperglycemia on the transendothelial migration of monocytes is not known. Exposure of human umbilical vein endothelial cells (HUVEC) cultured in a Transwell chamber to 25 mM D-glucose (a concentration representing a hyperglycemic state) for 2 h resulted in a twofold increase in the migration of vitamin D3-differentiated monocyte-like HL-60 cells. The migration was inhibited by addition of either an antibody to platelet-endothelial cell adhesion molecule-1 (PECAM-1) or a protein kinase C inhibitor, GF-109203X. In HUVEC, high concentrations of D-glucose (25 mM), but not of other sugars such as L-glucose, 2-deoxyglucose, D-galactose, or D-mannitol, caused a sevenfold increase in the phosphorylation of PECAM-1 as a result of activation of protein kinase C. The 25 mM D-glucose-induced PECAM-1 phosphorylation and transmigration of monocyte-like HL-60 cells were further increased by treatment of HUVEC with the phosphatase inhibitor calyculin A. These results suggest that direct phosphorylation of PECAM-1 in response to elevated glucose promotes transendothelial migration of monocytes, contributing to accelerated atherogenesis in diabetics.
Department of Biochemistry, University of Southern California, School of Medicine, Los Angeles 90033, USA.
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V
Rattan
Y
Y
Shen
C
C
Sultana
D
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Kumar
V K
VK
Kalra
D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D007158:Immunologic Techniques; D009000:Monocytes / Q000166:cytology*; D009005:Monosaccharides / Q000494:pharmacology; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology*; D014471:Umbilical Veins
D009005:Monosaccharides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011493:Protein Kinase C; D005947:Glucose