Cigarette smoke condensate induced adhesion molecule expression and
transendothelial migration of monocytes .
Shen, Yamin, Vinod Rattan, Chand Sultana, and Vijay K. Kalra.
Department of Biochemistry and Molecular Biology, University of
Southern California, School of Medicine, Los Angeles, California
90033
APStracts 2:0442H, 1995.
Cigarette smoking is clearly linked with increased incidence of
atherosclerosis and cardiovascular disease. The adherence of blood
monocytes to the endothelium, followed by their migration beneath the
endothelium, are initiating events in the formation of foam cells,
promoting atherogenesis. We show here that cigarette smoke condensate
(CSC)-induced surface expression of a subset of cell adhesion
molecules (CAM), ICAM-1, ELAM-1 and VCAM-1, in human umbilical vein
endothelial cells (HUVEC) is associated with an increase in the
binding activity of the transcription factor, NF-kB, to the consensus
motif common to the CAM genes. Furthermore, CSC (25 _g/ml) both
increases the rate of transendothelial migration of vitamin D3
-differentiated monocyte-like cells across the HUVEC monolayer by 200%
and causes a 10-fold increase, approximately, in the phosphorylation
of PECAM-1, an adhesion molecule located at intercellular junctions
and involved in endothelial cell-cell adhesion. Our results show that
CSC induced activation of protein kinase C in endothelial cells,
initiates a signaling pathway leading to heightened binding of NF-kB
to specific DNA sequences, in turn increasing surface expression of
subset of CAMs. Further, our studies demonstrate a link between the
phosphorylation of PECAM-1 and the migration of blood monocytes
across vascular endothelium.
Received 27 June 1995; accepted in final form 20 September 1995.
APS Manuscript Number H587-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95