Acute and progressive lung injury after contact with phorbol myristate acetate.

Because of its potent ability to activate leukocytes and macrophages, resulting in the generation of large amounts of oxygen products (O-2, H2O2), phorbol myristate acetate (PMA) has been instilled into the air-ways of rats. The resulting acute lung injury is dose-dependent on the amount of PMA employed, is chiefly confined anatomically to the alveolar and interstitial compartments, is neutrophil-independent, and can be inhibited by catalase but not by superoxide dismutase. These data suggest that the generation of H2O2 is major mechanism involved in this method of acute lung injury. It has also been demonstrated that a progressive pattern of lung injury develops after exposure to PMA, with the onset of an interstitial fibrotic reaction by the sixth day. These data reinforce our recent studies, in which both acute and progressive injury occurs in lungs of rats when H2O2 is generated.