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Red blood cell‐induced proinflammatory lung endothelial signaling in hypoxia
Author(s) -
Huertas Alice,
Das Shonit,
Lindert Jens,
Yiming Maimaiti,
Bhattacharya Sunita,
Bhattacharya Jahar
Publication year - 2009
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.23.1_supplement.1023.4
Subject(s) - hypoxia (environmental) , proinflammatory cytokine , lung , chemistry , inflammation , selectin , endothelial stem cell , microbiology and biotechnology , immunology , medicine , endocrinology , biology , biochemistry , in vitro , oxygen , organic chemistry
To determine endothelial (EC) mechanisms underlying hypoxia‐induced lung inflammation, we considered that red blood cell (RBC)‐derived H 2 O 2 diffuses to lung EC (Kiefmann. Blood. 2008). Hence, H 2 O 2 might induce proinflammatory signaling causing EC expression of the leukocyte adhesion receptor, E‐selectin. To test this possibility, we exposed isolated mouse lungs, perfused with RBC‐containing buffer to 4 hours of normoxia (21% O 2 ) or hypoxia (8% O 2 ). Then using our reported methods (Yiming. AJRCMB. 2008), we infused the pulmonary artery with chilled collagenase and trypsin to obtain 10 4 cells/lung in the left atrial effluent. We dual labeled the cells with fluorophore‐conjugated mAbs (10μg/ml) against E‐selectin as well as the EC marker, von Willebrand factor. Finally, using flow cytometry, we determined cell fluorescence. Exposing lungs to hypoxia increased EC E‐selectin three times above the normoxic control (p<0.05; n=3). Importantly, the H 2 O 2 hydrolyzing agent, catalase (50 U/ml) blocked the hypoxia‐induced E‐selectin enhancement (p<0.05, n=3). Moreover, in lungs perfused with RBC‐free buffer, hypoxia failed to increase EC E‐selectin above control (p<0.05, n=3). We conclude that in hypoxia, RBC‐derived H 2 O 2 activates E‐selectin expression in lung EC. These responses might underlie initiation of lung vascular inflammation (Support: HL36024).