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NFkB signaling and inducible nitric oxide synthase activity during pulmonary ischemia‐reperfusion increase co‐localization of fibrinogen/fibrin and platelets at sites of vascular leakage in rabbit lung
Author(s) -
Dixon James T,
Gozal Evelyne,
Sachleben Leroy R,
Lominadze David,
Juniel Charla L,
Roberts Andrew M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1130.14
Subject(s) - platelet , lung , nitric oxide synthase , fibrin , platelet activation , fibrinogen , chemistry , nitric oxide , pulmonary edema , pathology , medicine , immunology
Platelet adhesion and fibrinogen/fibrin (Fg/Fb) deposition cause endothelial dysfunction during acute lung injury. We examined the hypothesis that during pulmonary IR, platelet activation, recruitment of Fg/Fb to the vascular wall and subsequent leakage are associated with NFκB and inducible nitric oxide synthase (iNOS) activation pathways. Subpleural microvessels and alveoli were examined by video microscopy of the right lung in anesthetized rabbits with open chest and ventilated lungs. IR was caused by occluding the right pulmonary artery for 2 h. Injection of fluorescently labeled albumin and a polyclonal antibody to Fg/Fb into the pulmonary circulation via the right atrium during early reperfusion revealed areas of microvascular leakage and interstitial edema associated with Fg/Fb deposition. Platelets were detected by immunohistochemistry of tissue samples at sites of vascular leakage in conjunction with Fg/Fb. On average, IR (n=3) caused a 6–7 fold increase in albumin leakage, platelet adhesion, and albumin‐Fg/Fb‐platelet co‐localization compared to control. Additionally, IR increased NF‐κB activation in lung lysates as detected by phosphorylation of IκB. These effects were attenuated by treatment with an iNOS activity inhibitor (1400W) before IR. Our data suggest that NFκB and iNOS activation may play a critical role in the regulation of platelet Fg/Fb–induced microvascular leakage during pulmonary IR. Supported in part by American Lung Association‐Kentucky to AMR and NIH grant #HL080394 to DL.