title: Actin S-nitrosylation inhibits neutrophil beta2 integrin function.
abstract: The focus of this work was to elucidate the mechanism for inhibition of neutrophil beta(2) integrin adhesion molecules by hyperoxia. Results demonstrate that exposure to high oxygen partial pressures increases synthesis of reactive species derived from type 2 nitric-oxide synthase and myeloperoxidase, leading to excessive S-nitrosylation of beta-actin and possibly profilin. Hyperoxia causes S-nitrosylation of the four cysteine moieties closest to the carboxyl-terminal end of actin, which results in formation of short actin filaments. This alters actin polymerization, network formation, and intracellular distribution, as well as inhibits beta(2) integrin clustering. If neutrophils are exposed to ultraviolet light to reverse S-nitrosylation, or are incubated with N-formyl-methionyl-leucine-phenylalanine to trigger "inside-out" activation, the effects of hyperoxia are reversed. We conclude that cytoskeletal changes triggered by hyperoxia inhibit beta(2) integrin-dependent neutrophil adhesion.
authors.affiliation: Institute for Environmental Medicine, Department of Emergency Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104-6068, USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Thom
authors.forename: Veena M
authors.initials: VM
authors.lastname: Bhopale
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Mancini
authors.forename: Tatyana N
authors.initials: TN
authors.lastname: Milovanova
mesh_terms: D000199:Actins / Q000378:metabolism / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D018821:CD18 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D002448:Cell Adhesion; D018496:Hyperoxia; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D051304:Profilins / Q000378:metabolism
chemical_list: D000199:Actins; D018821:CD18 Antigens; D051304:Profilins; D009195:Peroxidase; D010100:Oxygen