title: Oxidant stress-induced transendothelial migration of monocytes is linked to phosphorylation of PECAM-1.
abstract: 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 increased 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 umbilical vein endothelial cells (HUVECs) causes a twofold increase in the transendothelial migration of monocyte-like HL-60 cells and a fivefold increase in platelet endothelial cell adhesion molecule-1 (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, p21ras and glutathione synthesis. However, treatment of HUVECs 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles 90033, USA.
authors.forename: V
authors.initials: V
authors.lastname: Rattan
authors.forename: C
authors.initials: C
authors.lastname: Sultana
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: V K
authors.initials: VK
authors.lastname: Kalra
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D008387:Marine Toxins; D009000:Monocytes / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D018384:Oxidative Stress; D010545:Peroxides / Q000494:pharmacology*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D011341:Probucol / Q000494:pharmacology; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D014471:Umbilical Veins; D014810:Vitamin E / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
chemical_list: D000911:Antibodies, Monoclonal; D000975:Antioxidants; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D008387:Marine Toxins; D010080:Oxazoles; D010545:Peroxides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; C077108:4-(2-hydroxyphenyl)-2-carboxy-3-pyrrolidineacetic acid; D014810:Vitamin E; C017759:9-(tetrahydro-2-furyl)-adenine; C059041:calyculin A; D020122:tert-Butylhydroperoxide; D000225:Adenine; C070515:bisindolylmaleimide I; D011341:Probucol; D007608:Kainic Acid