Tissue plasminogen activator inhibits reactive oxygen species production by macrophages.
OBJECTIVE
To determine whether tissue plasminogen activator (tPA) alters macrophage reactive oxygen species (ROS) production.


METHODS
Cultured macrophages were exposed to either phorbol myristate acetate (PMA) or zymosan (ZMA) after a 1-hour incubation with either tPA 100 microg/ml or L-arginine 3.5 mg/ml, an excipient used in the formulation of tPA.


RESULTS
Production of ROS was measured using chemiluminescence (CL). Tissue plasminogen activator reduced the mean peak CL of macrophages 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.


CONCLUSIONS
Our results suggest that tPA has broad inhibitory effects on inflammatory cell ROS production. In diseases such as atherosclerosis and acute respiratory distress syndrome, these data suggest the possible utility of exogenous tPA as an antiinflammatory agent and a physiologic role for endogenous tPA that goes beyond maintenance of homeostasis.
Stringer
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Department of Pharmacy Practice, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
D017382:Reactive Oxygen Species; D015054:Zymosan; D001120:Arginine; D010959:Tissue Plasminogen Activator; D013755:Tetradecanoylphorbol Acetate