Release of tumor necrosis factor after pulmonary artery occlusion and reperfusion.
Cytokines may function as mediators of reperfusion tissue injury in lungs. Because the lung contains resident macrophages that can serve as potential sources of cytokines, we examined the possibility that pulmonary artery occlusion by reperfusion is a factor in mediating the release of cytokines. After left lung ischemia induced by a 24-h period of left pulmonary artery occlusion, we observed a transient increase in TNF-alpha concentration in lung effluent in rabbits during the period reperfusion. The peak TNF-alpha levels ranged from 55 to 335 pg/ml, and a mean peak time was at 45 to 60 min after the initiation of reperfusion. The TNF-alpha concentrations then decreased towards baseline. TNF-alpha was detected in control plasma or in plasma from sham-operated animals. Less than 10 pg/ml of endotoxin was detected in any samples. Lung tissue myeloperoxidase content, a measure of neutrophil infiltration, increased progressively during the 2-h reperfusion period. The time course of generation of TNF-alpha preceded the maximal rise in lung tissue myeloperoxidase activity. The data show that lung ischemia/reperfusion results in transient generation of TNF-alpha, which is known to mediate neutrophil sequestration. Neutrophil sequestration and resulting lung injury after reperfusion may be dependent on generation of TNF-alpha at the onset of reperfusion.
Department of Physiology and Cell Biology, Albany Medical College, New York 12208.
G P
GP
Palace
P J
PJ
Del Vecchio
M J
MJ
Horgan
A B
AB
Malik
D000818:Animals; D003250:Constriction; D004731:Endotoxins / Q000032:analysis; D005260:Female; D008033:Limulus Test; D008168:Lung / Q000098:blood supply / Q000378:metabolism*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D011651:Pulmonary Artery / Q000502:physiology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase