title: Cigarette smoke condensate-induced adhesion molecule expression and transendothelial migration of monocytes.
abstract: 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 that cigarette smoke condensate (CSC)-induced surface expression of a subset of cell adhesion molecules (CAM) [intercellular adhesion molecule 1 (ICAM-1), endothelial leukocyte adhesion molecule 1 (ELAM-1), and vascular cell adhesion molecule 1 (VCAM-1)] in human umbilical vein endothelial cells (HUVEC) is associated with an increase in the binding activity of nuclear transcription factor NF-kappa B to the consensus motif common to the CAM genes. Furthermore, CSC (25 microgram/ml) both increases the rate of transendothelial migration of vitamin D3-differentiated monocyte-like cells across the HUVEC monolayer by 200% and causes an approximately 10-fold increases in the phosphorylation of platelet endothelial CAM (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 pathways, leading to heightened binding of NF-kappa B to specific DNA sequences, which in turn increases surface expression of the subset of CAMs. Furthermore, our studies demonstrate a link between the phosphorylation of PECAM-1 and the migration of blood monocytes across vascular endothelium.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles, 90033, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: V
authors.initials: V
authors.lastname: Rattan
authors.forename: C
authors.initials: C
authors.lastname: Sultana
authors.forename: V K
authors.initials: VK
authors.lastname: Kalra
mesh_terms: D000818:Animals; D001483:Base Sequence; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D015345:Oligonucleotide Probes / Q000235:genetics; D010766:Phosphorylation; D010947:Plants, Toxic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016328:NF-kappa B; D015345:Oligonucleotide Probes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012906:Smoke; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D011493:Protein Kinase C