Oxidant stress-induced transendothelial migration of monocytes is
linked to phosphorylation of pecam-1.
Rattan, Vinod, Chand Sultana, Yamin Shen, and Vijay K. Kalra.
Department of Biochemistry and Molecular Biology, University of
Southern California, School of Medicine, Los Angeles, CA 90033
APStracts 4:0100E, 1997.
Reactive oxygen species (ROS) are believed to cause vascular injury in
the pathophysiology of atherosclerosis, diabetes and vasoocclusion in
sickle cell disease. Studies have shown that ROS causes increase
adhesion of monocytes and neutrophils to the endothelium. We
investigated the effects of tert-butylhydroperoxide (t-BuOOH), an
inducer of oxidant stress, to determine the cellular signaling
pathway leading to the transendothelial migration of
polymorphonuclear leukocytes. Our studies revealed that signaling by
t-BuOOH in human endothelial cells (HUVEC) causes 2-fold increase in
the transendothelial migration of monocyte-like HL-60 cells and 5
-fold increase in PECAM-1 phosphorylation. The transmigration induced
by t-BuOOH was inhibited by an antibody to PECAM-1. These events were
inhibited by antioxidants, and inhibitors of protein kinase C (PKC),
p21ras and glutathione synthesis. However, treatment of HUVEC with
the phosphatase inhibitor Calyculin A augmented the t-BuOOH-mediated
transendothelial migration of monocytes and PECAM-1 phosphorylation.
Our results suggest that oxidative stress can induce the
transendothelial migration of monocytes as a result of
phosphorylation of PECAM-1, a crucial event in the diapedesis of
leukocytes during pathophysiology of vascular diseases.
Received 30 December 1996; accepted in final form 23 April 1997.
APS Manuscript Number E630-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 13 May 1997