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Thrombin activates calcium independent phospholipase A 2 (iPLA 2 ) in lung microvascular endothelial cells
Author(s) -
Rastogi Prerna,
McHowat Jane
Publication year - 2008
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.22.1_supplement.1178.6
Subject(s) - thrombin , arachidonic acid , stimulation , lung , antagonist , medicine , endocrinology , endothelium , biology , platelet , microbiology and biotechnology , chemistry , receptor , immunology , biochemistry , enzyme
The alveolar‐capillary barrier comprises of type 1 pneumocytes of the alveolar wall, endothelial cells of the capillaries and the basement membrane. Its function is to prevent blood entering the alveoli and to facilitate efficient gaseous exchange. Any disruption in the lining of the lung microveasculature is potentially deleterious. This study examines thrombin stimulation of human lung microvascular endothelial cells (HMVEC‐L) and the resultant increase in iPLA 2 activity. Incubation of HMVEC‐L with thrombin resulted in a fourfold increase in iPLA 2 activity that remained elevated for up to 60 minutes. Pretreatment of HMVEC‐L with bromoenol lactone (BEL, 2μM, 10 min, a selective iPLA 2 inhibitor) but not with PX‐18 (2μM, 10 min, an sPLA 2 inhibitor), or AACOCF 3 (2μM, 10 min, a cPLA 2 inhibitor) attenuated thrombin‐activated iPLA 2 . Activation of iPLA 2 resulted in a rapid increase in arachidonic acid and PGI 2 release that was also inhibited by BEL pretreatment. Thrombin stimulation also resulted in a four‐fold increase in neutrophil adherence to the apical surface of HMVEC‐L that was inhibited by BEL pretreatment of HMVEC‐L and pretreatment of the neutrophils with a PAF receptor antagonist. Taken together, these results demonstrate that iPLA 2 inhibition has the potential to block the several inflammatory responses produced by thrombin in the lung microvasculature. Supported by AHA, Pre‐Doctoral Fellowship (PR)