Tissue plasminogen activator inhibits reactive oxygen species production by macrophages

Study Objective. To determine whether tissue plasminogen activator (tPA) al ters macrophage reactive oxygen species (ROS) production. Intervention. Cultured macrophages were exposed to either phorbol myristate acetate (PMA) or zymosan (ZMA) after a 1-hour incubation with either tPA 1 00 mu g/ml or L-arginine 3.5 mg/ml, an excipient used in the formulation of tPA. Measurements and Main Results. Production of ROS was measured using chemilu minescence (CL). Tissue plasminogen activator reduced the mean peak CL of m acrophages exposed to PMA or ZMA by 20% and 36%, respectively (p=0.0008 and p=0.028, analysis of variance). L-arginine had no effect on either PMA- or ZMA-induced macrophage CL. Conclusion. Our results suggest that tPA has broad inhibitory effects on in flammatory cell ROS production. In diseases such as atherosclerosis and acu te respiratory distress syndrome, these data suggest the possible utility o f exogenous tPA as an antiinflammatory agent and a physiologic role for end ogenous tPA that goes beyond maintenance of homeostasis.