Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury.
BACKGROUND
The mechanism by which stimulated neutrophils (polymorphonuclear leukocytes [PMNs]) damage pulmonary vascular endothelium was investigated.


METHODS
The ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability was tested. Each series was conducted on 6 rats. To stimulate PMNs, they were agitated gently in a glass vial for 10 seconds.


RESULTS
Perfusing lungs with the stimulated PMNs elicited a fivefold increase in permeability compared with lungs perfused with the unstimulated cells. This increase in permeability was blocked completely by preincubation of stimulated PMNs with CD18 monoclonal antibody. This increase in permeability was also blocked completely by superoxide dismutase (SOD) or the xanthine oxidase (XO) inhibitor allopurinol. Pulmonary vascular hemodynamics were unaffected by any treatment protocol. The accumulation of stimulated PMNs within the lungs was not inhibited by SOD but was partially blocked by allopurinol.


CONCLUSIONS
These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration resulted from endothelial cell injury caused by superoxide anion possibly generated by XO, exclusively present in the endothelial cells.
Tanita
T
T
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. tanita@idac.tohoku.ac.jp
Song
C
C
Kubo
H
H
Hoshikawa
Y
Y
Ueda
S
S
Fujimura
S
S
D000818:Animals; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply* / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009195:Peroxidase