Cyclooxygenase metabolites possibly produced by endothelial cells mediate the lung injury caused by mechanically stimulated leukocytes.
To determine whether mechanically stimulated leukocytes increase pulmonary vascular permeability and resistance and, if so, whether cyclooxygenase metabolites mediate the increase, we assessed the effects of stimulated and unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular permeability and resistance in isolated perfused lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentle agitation in a glass container for 10 seconds. After baseline measurements were made, stimulated or unstimulated leukocytes were added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and pulmonary vascular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of leukocytes to the pulmonary vascular endothelium. These findings suggest that mechanically stimulated leukocytes increase pulmonary vascular permeability and that cyclooxygenase metabolites produced by endothelial cells may injure the cells.
Tanita
T
T
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. tanita@idac.tohoku.ac.jp
Ueda
S
S
Chun
S
S
Hoshikawa
Y
Y
Noda
M
M
Kubo
H
H
Suzuki
S
S
Ono
S
S
Fujimura
S
S
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism* / Q000502:physiology; D008168:Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010477:Perfusion / Q000295:instrumentation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D014655:Vascular Resistance / Q000187:drug effects
D008469:Meclofenamic Acid; D011451:Prostaglandin-Endoperoxide Synthases