ActinS-Nitrosylation Inhibits Neutrophil β2Integrin Function

Stephen R. Thom, Veena M. Bhopale, D. Joshua Mancini, Tatyana N. Milovanova
2008 Journal of Biological Chemistry  
The focus of this work was to elucidate the mechanism for inhibition of neutrophil ␤ 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 ␤-actin and possibly profilin. Hyperoxia causes S-nitrosylation of the four cysteine moieties closest to the carboxyl-terminal end of actin, which results in
more » ... which results in formation of short actin filaments. This alters actin polymerization, network formation, and intracellular distribution, as well as inhibits ␤ 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 "insideout" activation, the effects of hyperoxia are reversed. We conclude that cytoskeletal changes triggered by hyperoxia inhibit ␤ 2 integrin-dependent neutrophil adhesion.
doi:10.1074/jbc.m709200200 pmid:18283105 fatcat:vo3ruffbxrgn5n4jsi5y2y57jq