Glucose-induced transmigration of monocytes is linked to
phosphorylation of pecam-1 in cultured endothelial cells.
Rattan, Vinod, Yamin Shen, Chand Sultana, Dinesh Kumar, and Vijay K.
Kalra.
Department of Biochemistry and Molecular Biology, and Department of
Medicine, University of Southern California, School of Medicine, Los
Angeles, California 90033
APStracts 3:0134E, 1996.
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 Transwell chamber to 25 mM D
-glucose (a concentration representing a hyperglycemic state) for 2 h
resulted in a 2-fold 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 (PECAM-1), or by 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 7-fold 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.
Received 14 December 1995; accepted in final form 26 June 1996.
APS Manuscript Number E583-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996