PMID: 9179619Feb 1, 1997Paper

Tissue plasminogen activator (tPA) inhibits human neutrophil superoxide anion production in vitro

Inflammation
K A StringerJ E Repine

Abstract

Because neutrophils contribute to reperfusion injury associated with acute myocardial infarction (MI), and because tissue plasminogen activator (tPA) is often used in the management of MI, we evaluated the effect of tPA on superoxide (O2.-) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced O2.- generation by neutrophils treated with phorbol myristate acetate (PMA) in vitro. Furthermore, adding tPA that had been previously treated with the protease inhibitor, D-Phe-Pro-Arg-chloromethyl ketone HCl (PPACK), also decreased neutrophil O2.- generation in vitro (P < 0.05). In contrast, adding L-arginine, a component of the tPA preparation and a precursor of nitric oxide (NO), did not inhibit PMA-induced neutrophil O2.- production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of O2.- produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil O2.- generation by a mechanism that is not related to L-arginine, is not dependent on tPA proteolytic activity, and is not a function of direct scavenging. This property may account for some of the effectiveness of tPA i...Continue Reading

Citations

Sep 27, 2008·Annals of Tropical Medicine and Parasitology·I NuchprayoonN Sripaiboonkij
Sep 24, 2005·Pharmaceutical Research·John S DunnKathleen A Stringer
Oct 10, 2008·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Joris J T H RoelofsSandrine Florquin
Dec 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michal J SeredaCatherine Vial
Mar 10, 2000·American Journal of Physiology. Heart and Circulatory Physiology·S Bertuglia, A Colantuoni
Jun 12, 2004·Clinical and Experimental Pharmacology & Physiology·Kathleen A StringerDaniel L Gustafson
Aug 2, 2008·Clinical and Experimental Pharmacology & Physiology·Kathleen A StringerRajiv Nayar
Nov 18, 2005·Journal of the American Society of Nephrology : JASN·Joris J T H RoelofsSandrine Florquin
Jul 17, 1998·Free Radical Biology & Medicine·K A StringerJ E Repine

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