Procoagulant and fibrinolytic properties of bovine endothelial cells treated with monocrotaline pyrrole.
Administration to rats of monocrotaline pyrrole (MCTP), a putative metabolite of the pyrrolizidine alkaloid, monocrotaline, causes pulmonary microvascular thrombosis that is associated with vascular remodeling and pulmonary hypertension. It is possible that vascular thrombi contribute to the lesions that occur after MCTP treatment. Since MCTP is toxic to pulmonary endothelial cells and because the pulmonary endothelium is in a unique position to influence procoagulant and fibrinolytic reactions in the lungs, we examined changes in the procoagulant and fibrinolytic properties of cultured pulmonary artery endothelial cells exposed to MCTP to see if they might favor thrombosis. Monolayers of confluent bovine pulmonary arterial endothelial cells received a single administration of MCTP or N,N-dimethylformamide vehicle, and the media or lysates were examined at 4, 24, 48, or 120 hr after treatment. MCTP caused a time-dependent cell detachment and an increase in release of lactate dehydrogenase into culture medium. Although cell numbers decreased dramatically with time, the protein concentration of cell monolayer lysates was unchanged by treatment. MCTP treatment caused no change in the amount of tissue factor activity/micrograms cellular protein in bovine endothelial cell lysates and only a small increase in the activity of Factor V in the culture medium at 120 hr. In addition, the medium from bovine endothelial cells treated with MCTP had a time-dependent increase in the activity of plasminogen activators and a decrease in the activity of plasminogen activator inhibitors. Thus bovine endothelial cells exposed to MCTP in vitro do not produce changes in these procoagulant or fibrinolytic properties that would explain the thrombosis observed in vivo.
Department of Pathology, Michigan State University, East Lansing 48824.
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AE
Schultze
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RA
Roth
D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002417:Cattle; D002452:Cell Count / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004126:Dimethylformamide / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005165:Factor V / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016686:Monocrotaline / Q000031:analogs & derivatives* / Q000633:toxicity; D010960:Plasminogen Activators / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism
D001779:Blood Coagulation Factors; D003470:Culture Media; D015849:Plasminogen Inactivators; C014114:monocrotaline pyrrole; D016686:Monocrotaline; D004126:Dimethylformamide; D005165:Factor V; D013925:Thromboplastin; D007770:L-Lactate Dehydrogenase; D010960:Plasminogen Activators