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Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury
1Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan. tanita@idac.tohoku.ac.jp
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.
Insights
Stimulated neutrophils (polymorphonuclear leukocytes) increase lung vascular permeability via superoxide anion generated by xanthine oxidase in endothelial cells. This injury mechanism is blocked by CD18 antibodies, superoxide dismutase, and allopurinol.
Area of Science:
- Pulmonary medicine
- Immunology
- Cellular biology
Background:
- Investigating the mechanism of pulmonary vascular endothelium damage by stimulated neutrophils (polymorphonuclear leukocytes, PMNs).
- Understanding the role of PMN adhesion in altering pulmonary vascular permeability.
Purpose of the Study:
- To determine how stimulated PMNs damage pulmonary endothelial cells.
- To identify the molecular mediators involved in PMN-induced lung vascular injury.
Main Methods:
- Mechanically stimulated and unstimulated PMNs were tested for adherence to pulmonary endothelial cells in rats.
- Pulmonary vascular permeability was measured after perfusion with PMNs.
- Inhibitors like CD18 monoclonal antibody, superoxide dismutase (SOD), and allopurinol were used to block effects.
Main Results:
- Stimulated PMNs increased lung vascular permeability fivefold compared to unstimulated PMNs.
- This increase was blocked by CD18 antibody, SOD, and allopurinol.
- PMN accumulation was not affected by SOD but partially blocked by allopurinol.
Conclusions:
- Stimulated PMN-induced pulmonary vascular filtration increase results from endothelial cell injury.
- Superoxide anion, possibly generated by xanthine oxidase (XO) in endothelial cells, mediates this injury.
- Findings suggest XO-derived superoxide is a key factor in PMN-induced lung vascular damage.