NEUTROPHIL-GENERATED FREE-RADICALS - POSSIBLE MECHANISMS OF INJURY INADULT-RESPIRATORY-DISTRESS-SYNDROME

The acute lung injury resulting from adult respiratory distress syndro me (ARDS) is thought to be largely mediated by activated neutrophils. Because activated neutrophils produce the superoxide radical, which is both bactericidal and cytotoxic to host cells, this oxygen-derived fr ee radical is likely responsible for at least part of the neutrophil-m ediated lung injury. In a rat model of ARDS resulting from intratrache al instillation of interleukin-1, recombinant human manganous superoxi de dismutase significantly decreased lung leak. One detrimental action of proteases released by adherent neutrophils may be the degradation of extracellular superoxide dismutase (ECSOD), which normally binds to the heparan sulfate on the surface of the endothelium. We found that rabbit ECSOD incubated with either trypsin or activated neutrophils lo ses affinity for heparin. Furthermore, soluble ECSOD is elevated in th e serum of patients with ARDS, consistent with this hypothesis.