Neutrophil elastase augments acute edematous injury in isolated rat lungs perfused with neutrophil cytoplasts.

To assess the contribution of neutrophil elastase to neutrophil-mediated acute edematous lung injury, isolated rat lungs were perfused with human neutrophil cytoplasts that produce O2 metabolites normally but contain little of the neutrophil elastase usually found in neutrophils. We found that addition of neutrophil cytoplasts and phorbol myristate acetate (PMA) caused less edematous injury in isolated lungs than addition of neutrophils and PMA. However, addition of neutrophil elastase along with neutrophil cytoplasts and PMA increased the amounts of lung injury found in lungs perfused with neutrophil cytoplasts and PMA to levels that equaled the amount of lung injury found after addition of normal neutrophils and PMA. By comparison, addition of purified neutrophil elastase, PMA alone, or human neutrophils alone did not cause lung injury. The results indicate that neutrophil elastase is a necessary component for the maximal development of acute edematous injury in isolated lungs perfused with neutrophils and PMA.