CYCLOOXYGENASE METABOLITES POSSIBLY PRODUCED BY ENDOTHELIAL-CELLS MEDIATE THE LUNG INJURY CAUSED BY MECHANICALLY STIMULATED LEUKOCYTES

To determine whether mechanically stimulated leukocytes increase pulmo nary vascular permeability and resistance and, if so, whether cyclooxy genase metabolites mediate the increase, me assessed the effects of st imulated and unstimulated leukocytes, and of a cyclooxygenase inhibito r on pulmonary vascular permeability and resistance in isolated perfus ed lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentl e agitation in a glass container for 10 seconds. After baseline measur ements mere made, stimulated or unstimulated leukocytes mere added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenam ate, on the pulmonary vascular filtration coefficient and pulmonary va scular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vasc ular resistance were about 2.5 times and 3.3 times higher, respectivel y, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histol ogical examination indicated that meclofenamate did not prevent the ad hesion of leukocytes to the pulmonary vascular endothelium. These find ings suggest that mechanically stimulated leukocytes increase pulmonar y vascular permeability and that cyclooxygenase metabolites produced b y endothelial cells may injure the cells. (C) 1997 Tohoku University M edical Press.