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http://purl.uniprot.org/citations/21474822http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21474822http://www.w3.org/2000/01/rdf-schema#comment"

Objective

The goal of this study was to determine whether tumor necrosis factor α (TNFα)-induced Src activation and intercellular adhesion molecule-1 (ICAM-1) phosphorylation rapidly increase endothelial cell adhesivity and polymorphonuclear leukocyte (PMN) sequestration independently of de novo ICAM-1 synthesis.

Methods and results

TNFα exposure of mouse lungs for 5 minutes produced a 3-fold increase in (125)I-anti-ICAM-1 monoclonal antibody (mAb) binding and (111)In oxine-labeled PMN sequestration, as well as Src activation, ICAM-1 Tyr518 phosphorylation, and phospho-Tyr518-ICAM-1 coimmunoprecipitation with actin. The response was absent in Nox2(-/-) lungs or following Src inhibition. In COS-7 cells transfected with wild-type (WT), phospho-defective (Tyr518Phe), or phospho-mimicking (Tyr518Asp) mouse ICAM-1 cDNA constructs, TNFα increased the B(max) of YN1/1.7.4 anti-ICAM-1 mAb binding to WT-ICAM-1 but not to Tyr518Phe-ICAM-1, indicating increased binding avidity secondary to ICAM-1 phosphorylation. This effect was mimicked by expression of the Tyr518Asp-ICAM-1 mutant. TNFα also increased the staining intensity and cell surface clustering of YN1/1.7.4 mAb-labeled WT-ICAM-1 that colocalized with F-actin, which was not observed with Tyr518Phe-ICAM-1 but was recapitulated with Tyr518Asp-ICAM-1. Finally, overexpression of ICAM-1 in mouse lungs significantly increased lipopolysaccharide-induced transvascular albumin leakage and bronchoalveolar lavage PMN counts at 2 and 24 hours after lipopolysaccharide inhalation compared with lungs expressing the Tyr518Phe ICAM-1 mutant.

Conclusion

Src-dependent phosphorylation of endothelial cell ICAM-1 Tyr518 induces PMN adhesion by promoting ICAM-1 clustering, which we propose mediates rapid-phase lung vascular accumulation of PMNs during inflammation."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.110.222208"xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Gao X."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Hu G."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Liu G."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Danilov S.M."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Malik A.B."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Minshall R.D."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Javaid K."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/author"Vogel S.M."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/pages"1342-1350"xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/title"Src phosphorylation of endothelial cell surface intercellular adhesion molecule-1 mediates neutrophil adhesion and contributes to the mechanism of lung inflammation."xsd:string
http://purl.uniprot.org/citations/21474822http://purl.uniprot.org/core/volume"31"xsd:string
http://purl.uniprot.org/citations/21474822http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21474822
http://purl.uniprot.org/citations/21474822http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21474822
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