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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/L178    most recent 00263.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hu, G. Articles by Minshall, R. D. Search for Related Content PubMed PubMed Citation Articles by Hu, G. Articles by Minshall, R. D.

EDITORIAL FOCUS

Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury

Departments of ¹Pharmacology and ²Anesthesiology and ³Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois; and ⁴Herman B. Wells Center for Pediatric Research, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, Indiana

Submitted 6 July 2007 ; accepted in final form 6 November 2007

Caveolin-1 present in immune cells may be involved in regulation of the inflammatory response. Here, using caveolin-1-null (Cav-1^–/–) mice, we addressed the role of caveolin-1 in polymorphonuclear neutrophils (PMNs) in regulating PMN activation-mediated lung injury. In lungs of wild-type (Cav-1^+/+) mice perfused at constant flow with Krebs-Henseleit solution, addition of Cav-1^+/+ PMNs (4 x 10⁶ cells) into the perfusate followed by their activation with formyl-Met-Leu-Phe (fMLP, 1.0 µM) plus platelet-activating factor (1.0 nM) increased pulmonary microvessel filtration coefficient by 150% and wet-to-dry lung weight ratio by 50% as well as PMN accumulation in lungs. These responses were markedly reduced in lungs perfused with Cav-1^–/– PMNs followed by addition of the same activating agents. fMLP-stimulated adhesion of Cav-1^–/– PMNs to pulmonary microvascular endothelial cells and migration of Cav-1^–/– PMNs across endothelial monolayers were also impaired compared with Cav-1^+/+ PMNs. Cav-1^–/– PMNs showed 50–80% reduction in PMA- or fMLP-stimulated superoxide production compared with Cav-1^+/+ PMNs. In addition, Cav-1^–/– PMNs had decreased migratory activity (50%) and adhesion to fibrinogen (40%) in response to fMLP. Rac1 and Rac2 were activated in Cav-1^+/+ PMNs after stimulation of fMLP but not in Cav-1^–/– PMNs. Exogenous expression of caveolin-1 in COS-phox cells augmented the fMLP-induced Rac1 activation and superoxide production, indicating a direct role of caveolin-1 in the mechanism of superoxide production. Thus caveolin-1 expression in PMNs plays a key role in mediating PMN activation, adhesion, and transendothelial migration and in PMN activation-induced lung inflammation and vascular injury.

caveolae; permeability; edema; Rac