Thromboxane Synthesis by Sources Other Than Platelets in Association with Complement-Induced Pulmonary Leukostasis and Pulmonary Hypertension in Sheep

Infusion into sheep of plasma containing zymosan-activated complement produces leukopenia, pulmonary leukostasis, and pulmonary artery hypertension. We previously demonstrated a close relationship between the pulmonary vascular response and elevations of plasma thromboxane. We have investigated the...

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Bibliographic Details
Published in:Circulation research 1983-01, Vol.52 (1), p.1-6
Main Authors: McDonald, J W.D, Ali, M, Morgan, E, Townsend, E R, Cooper, J D
Format: Article
Language:English
Subjects:
6-Ketoprostaglandin F1 alpha - biosynthesis
Animals
Aspirin - pharmacology
Blood Platelets - metabolism
Complement Activation
Female
Hypertension, Pulmonary - immunology
Hypertension, Pulmonary - metabolism
In Vitro Techniques
Leukocytes - immunology
Lung - immunology
Lung - metabolism
Male
Pulmonary Artery - metabolism
Sheep
Thrombocytopenia - metabolism
Thromboxane B2 - biosynthesis
Thromboxanes - biosynthesis
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Summary:Infusion into sheep of plasma containing zymosan-activated complement produces leukopenia, pulmonary leukostasis, and pulmonary artery hypertension. We previously demonstrated a close relationship between the pulmonary vascular response and elevations of plasma thromboxane. We have investigated the source of thromboxane synthesis in this model. Plasma containing zymosan-activated complement added to whole blood did not stimulate thromboxane synthesis. This observation suggested that leukocytes do not synthesize thromboxane directly in response to complement. Sheep rendered severely thrombocytopenic by the administration of antiplatelet serum responded to complement infusion in the usual way. Pretreatment with aspirin (10 mg/kg) protected sheep against the pulmonary vascular response and completely blocked thromboxane synthesis. Transfusion of functional platelets did not restore these responses. Twentyfour hours after aspirin treatment, in vivo thromboxane synthesis was significantly greater than platelet thromboxane synthesis in vitro. Thromboxane is synthesized by a tissue which recovers cyclooxygenase enzyme activity at a rate that is more rapid than platelet turnover. Sheep lung synthesizes thromboxane actively in vitro. It is postulated that leukocytes exposed to activated complement components damage pulmonary vascular endothelial cells and stimulate synthesis of thromboxane A2 which causes pulmonary vasoconstriction.
ISSN:0009-7330
1524-4571
DOI:10.1161/01.RES.52.1.1