Thromboxane Modulates Endothelial Permeability

[摘要] The study tests the role of thromboxane in modulating microvascularpermeabilityin vitro. Cultured monolayers of bovineaortic endothelial cells were challenged with the thromboxane (Tx)mimic U46619. This led to disassembly of actin microfilaments, cellrounding, border retraction and interendotheHal gap formation.Pretreatment with the Tx receptor antagonist SQ 29,548 prevented theTx mimic-induced cytoskeletal changes. The Tx mimic also alteredendothelial cell barrier function. Increased permeability wasindicated by the increased passage of labelled albumin acrossmonolayers cultured on microcarriers, relative to untreatedendothelial cells (p<0.05). Furthermore, electron microscopyof endothelial cells cultured on the basement membrane of humanplacental amnion indicated increased permeability based on wide,interendotheHal gap formation and transit of the tracer horseradishperoxidase. Quantification of interendothelial gaps revealed aneleven-fold increase with the Tx mimic relative to untreatedendothial cells (p<0.05) and prevention by pretreatment withthe Tx receptor antagonist (p<0.05). These data indicate thatTx directly modulates the permeability of endothelial cellinvitro.

[学科分类] 生理学与病理学