title: Hydrogen peroxide-induced increase in endothelial adhesiveness is dependent on ICAM-1 activation.
abstract: Reactive oxygen radicals (ROS) generated by phagocytes promote human polymorphonuclear leukocyte (PMN) adhesion to human umbilical vein endothelial cells (EC). We determined the effects of hydrogen peroxide (H2O2), a phagocyte-derived ROS, on EC adhesiveness by determining steady-state intracellular adhesion molecule 1 (ICAM-1) mRNA and ICAM-1 protein expression. The adhesion of PMN to H2O2-treated EC was concentration dependent with maximal adhesion achieved at 0.1 mM H2O2. PMN adhesion occurred rapidly, reaching its maximum value within a 1-h treatment time. The PMN adhesion was dependent on the interaction between CD11/CD18 integrins on PMN and ICAM-1 on EC, since either anti-CD18 or anti-ICAM-1 monoclonal antibodies (MAbs) inhibited (by > 90%) the adhesive interaction between PMN and EC. In parallel with the increases in EC adhesivity, we detected a two- to threefold increase in EC surface expression of ICAM-1 between 0.5 and 1 h after H2O2 challenge. Northern analysis revealed an increase in the steady-state ICAM-1 mRNA signal within 0.5 h after H2O2 exposure, and the response was sustained up to 2 h. Inhibition of intracellular catalase in H2O2-treated EC by 3-amino-1,2,3-triazole augmented the PMN adhesion by 20%, whereas enhancement of EC H2O2-scavenging activity by addition of catalase abrogated the H2O2-induced PMN adhesion, indicating that oxidant-antioxidant balance at the EC interface is a critical factor modulating PMN-EC adhesive interactions. The results suggest that H2O2-induced PMN adhesion is dependent on the rapid induction of the ICAM-1 mRNA signal and the surface expression of ICAM-1 on EC.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
authors.forename: S K
authors.initials: SK
authors.lastname: Lo
authors.forename: K
authors.initials: K
authors.lastname: Janakidevi
authors.forename: L
authors.initials: L
authors.lastname: Lai
authors.forename: A B
authors.initials: AB
authors.lastname: Malik
mesh_terms: D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology; D015152:Blotting, Northern; D018821:CD18 Antigens; D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D012313:RNA; D006861:Hydrogen Peroxide; D002374:Catalase