Complement and neutrophil-mediated injury of perfused rat lungs.
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| Abstract |
It has previously been shown that systemic complement activation in rats leads to acute lung injury. We have now employed an ex vivo model of perfused rat lung which allows a more detailed examination of the role of circulating blood elements and pulmonary vascular pressure changes in the acute lung injury that occurs following cobra venom factor (CVF)-induced complement activation. In whole blood perfused lungs CVF infusion resulted in lung leukocyte sequestration, pulmonary vascular constriction, and acute lung injury. Lung injury was measured by quantitating the accumulation of [125I]-bovine serum albumin in lung parenchyma and alveolar lavage fluid. A histologic analysis of CVF-induced lung injury revealed the development of intravascular aggregates of platelets and accumulation of neutrophils, extensive bleb formation of pulmonary capillary interstitial endothelial cells, and interstitial and intraalveolar edema and intraalveolar hemorrhage. Experiments in lungs perfused with salt solution to which various blood elements were added showed that the development of lung injury was dependent on neutrophils and the interaction of CVF with heat-labile plasma components. The lung injury was not dependent on the presence of platelets or the pulmonary artery pressor response. Addition of catalase or erythrocytes to the lung perfusate significantly attenuated the acute lung injury. Like the development of lung injury, the pulmonary artery pressor response was dependent on the interaction of CVF with heat labile plasma components and neutrophils. The increase in PA pressure was not attenuated by the addition of catalase to the lung perfusate. These studies suggest that intravascular activation of the complement system leads to an acute microvascular injury which is dependent on neutrophils and the production of toxic oxygen metabolites. Pulmonary vascular constriction occurs independently of the associated lung injury and does not appear to be dependent on hydrogen peroxide production.
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| Authors | M L Morganroth, G O Till, R G Kunkel, P A Ward |
| Journal | Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 54 Issue 5 Pg. 507-14 (May 1986) ISSN: 0023-6837 [Print] United States |
| PMID | 3702342 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
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