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Tissue plasminogen activator inhibits reactive oxygen species production by macrophages
1Department of Pharmacy Practice, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Study Objective:
To determine whether tissue plasminogen activator (tPA) alters 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 100 microg/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 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.
Conclusion:
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.
Insights
Tissue plasminogen activator (tPA) significantly reduces reactive oxygen species (ROS) production in macrophages. These findings suggest tPA may serve as an anti-inflammatory agent in various diseases.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Macrophages are key inflammatory cells.
- Reactive oxygen species (ROS) play a role in inflammation.
- Tissue plasminogen activator (tPA) is primarily known for its role in hemostasis.
Purpose of the Study:
- To investigate the effect of tPA on macrophage ROS production.
- To determine if tPA has anti-inflammatory properties.
Main Methods:
- Macrophages were cultured and incubated with tPA or L-arginine.
- Stimulation of ROS production was induced using phorbol myristate acetate (PMA) or zymosan (ZMA).
- ROS production was quantified using chemiluminescence (CL).
Main Results:
- tPA significantly reduced PMA-induced ROS production by 20% (p=0.0008).
- tPA significantly reduced ZMA-induced ROS production by 36% (p=0.028).
- L-arginine, an excipient, had no effect on ROS production.
Conclusions:
- tPA exhibits broad inhibitory effects on inflammatory cell ROS production.
- Exogenous tPA may be useful as an anti-inflammatory agent in conditions like atherosclerosis and acute respiratory distress syndrome.
- Endogenous tPA may have a physiological role in regulating inflammation beyond hemostasis.