Suppression by isoproterenol of endothelial cell morphology and barrier function changes induced by platelet-activating factor.
Using a model to study vascular permeability on hydrostatically perfused bovine pulmonary artery endothelial cell (EC) monolayers and software to analyze cell morphological parameters automatically in a computer image workstation, we studied the effects of isoproterenol (IPN) on platelet-activating factor (PAF)-induced changes in EC monolayer permeability and cell morphological parameters. Albumin has fortifying effects on endothelial barrier function. As albumin concentration in the perfusate increased (0, 1, 5, 10, 20 mg/ml), EC monolayer hydraulic conductivity (Lp) decreased gradually while Lp of the filter membranes did not change. After treatment of the EC monolayer with PAF 10(-8) mol/liter for 30 min, transmonolayer fluid flow, protein clearance rate, and Lp value increased noticeably. At the same time, cell area decreased and intercellular distance and percentage of intercellular space area in total cell monolayer increased. Pretreatment with 10(-4) mol/liter IPN blocked PAF-induced EC permeability and morphological changes, suggesting that EC contraction and intercellular gap formation are important mechanisms for PAF-induced high vascular permeability. IPN inhibits the effects of PAF via stabilization of EC morphology, protection of intercellular junction, and blockade of intercellular gap formation.
Department of Pathophysiology, Second Military Medical University, Shanghai, P.R. China.
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Ding
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Li
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Jiang
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Wu
D000418:Albumins / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005780:Gelatin; D007091:Image Processing, Computer-Assisted; D007365:Intercellular Junctions / Q000187:drug effects / Q000648:ultrastructure; D007545:Isoproterenol / Q000494:pharmacology*; D008567:Membranes, Artificial; D010477:Perfusion / Q000295:instrumentation; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011651:Pulmonary Artery
D000418:Albumins; D008567:Membranes, Artificial; D010972:Platelet Activating Factor; D005780:Gelatin; D007545:Isoproterenol