title: Exogenous xanthine promotes neutrophil adherence to cultured endothelial cells.
abstract: Oxidants generated by endothelial xanthine oxidase (XO) can help trigger free radical-mediated tissue injury. An important event in oxidant-mediated tissue injury is neutrophil-endothelial adhesion. Although activation of endothelial XO increases adhesion, little is known about xanthine in the adhesive effect of XO. This study examined administered xanthine on the adhesion of neutrophils. Endothelial [human umbilical vein endothelial cells (HUVEC)] monolayers were exposed to xanthine (15 min), and neutrophils were allowed to adhere to HUVEC in an adhesion assay. Adhesion was dose dependently increased by xanthine (3-100 microM). Either catalase (1,000 U/ml), oxypurinol (XO inhibitor; 100 microM), or platelet-activating factor (PAF) receptor antagonist (WEB 2086; 10 microM) reduced neutrophil adhesion. Superoxide dismutase (1,000 U/ml) had no effect. Pretreatment of HUVEC with 50 microM tungsten also blocked xanthine-induced adherence. Adhesion was also inhibited by preincubation with 100 U/ml heparin. Finally, anti-P-selectin antibody (PB1.3; 20 micrograms/ml) attenuated adhesion. Our results indicate that xanthine may promote neutrophil-endothelial adhesion via a hydrogen peroxide- and PAF-mediated P-selectin expression.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport 71130, USA.
authors.forename: H
authors.initials: H
authors.lastname: Ichikawa
authors.forename: R E
authors.initials: RE
authors.lastname: Wolf
authors.forename: T Y
authors.initials: TY
authors.lastname: Aw
authors.forename: N
authors.initials: N
authors.lastname: Ohno
authors.forename: L
authors.initials: L
authors.lastname: Coe
authors.forename: D N
authors.initials: DN
authors.lastname: Granger
authors.forename: T
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: J S
authors.initials: JS
authors.lastname: Alexander
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D009994:Osmolar Concentration; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D014970:Xanthines / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001381:Azepines; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; D014970:Xanthines; C039351:platelet activating factor receptor; C052518:WEB 2086; D019820:Xanthine; D006493:Heparin; D014969:Xanthine Oxidase