Superoxide anion production by rat neutrophils at various stages of bleomycin-induced lung injury.

This study investigated the level of activation of neutrophils isolated from rats at various stages of bleomycin-induced lung injury. Neutrophils were collected from blood and bronchoalveolar lavage (BAL) fluid and their superoxide anion (O2-)-generating capacity measured in response to phorbol myristate acetate (PMA) and opsonized zymosan (OZ) stimulation. When stimulated with PMA, BAL neutrophils isolated from animals 3 days after bleomycin treatment had a significantly greater capacity to produce O2- than BAL neutrophils from animals 7 days after bleomycin treatment. The O2- levels of 7 day BAL neutrophils more closely resembled the resting levels obtained with circulating neutrophils from both control and bleomycin-treated animals. There were no differences observed in any of the neutrophils when stimulated with OZ. Myeloperoxidase levels were measured in plasma and BAL and found to be elevated only in plasma at 7 days after bleomycin. These data demonstrate that neutrophil activation does occur in this model and that the activation appears to be transient, in response to specific stimuli and compartmentalized between the lung and blood.