THROMBOXANE MODULATES ENDOTHELIAL PERMEABILITY

This study tests the role of thromboxane in modulating microvascular p ermeability in vitro. Cultured monolayers of bovine aortic endothelial cells were challenged with the thromboxane (Tx) mimic U46619. This le d to disassembly of actin microfilaments, cell rounding, border retrac tion and interendothelial gap formation. Pretreatment with the Tx rece ptor antagonist SQ 29,548 prevented the Tx mimic-induced cytoskeletal changes. The Tx mimic also altered endothelial cell barrier function. Increased permeability was indicated by the increased passage of label led albumin across monolayers cultured on microcarriers, relative to u ntreated endothelial cells (p < 0.05). Furthermore, electron microscop y of endothelial cells cultured on the basement membrane of human plac ental amnion indicated increased permeability based on wide, interendo thelial gap formation and transit of the tracer horseradish peroxidase . Quantification of interendothelial gaps revealed an eleven-fold incr ease with the Tx mimic relative to untreated endothial cells (P < 0.05 ) and prevention by pretreatment with the Tx receptor antagonist (p < 0.05). These data indicate that Tx directly modulates the permeability of endothelial cells in vitro.