Tissue Plasminogen Activator (tPA) Inhibits Human Neutrophil Superoxide Anion Production in Vitro期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

Tissue Plasminogen Activator (tPA) Inhibits Human Neutrophil Superoxide Anion Production in Vitro

Authors:	Kathleen A. Stringer Joann Lindenfeld Alexander J. Repine Zoe Cohen John 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 ( ${text{O}}_{{text{2}} cdot }^--$ ) production by human neutrophils in vitro. We found that adding increasing amounts of tPA significantly (r = 0.89, P < 0.025) and progressively reduced ${text{O}}_{{text{2}} cdot }^--$ 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 ${text{O}}_{{text{2}} cdot }^--$ 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 ${text{O}}_{{text{2}} cdot }^--$ production. Also, adding increasing concentrations of tPA did not reduce (P > 0.05) the concentrations of ${text{O}}_{{text{2}} cdot }^--$ produced by xanthine oxidase (XO) in vitro. Our findings suggest that tPA reduces neutrophil ${text{O}}_{{text{2}} cdot }^--$ 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 in the treatment of MI and/or make tPA valuable for treating acute respiratory distress syndrome (ARDS) or other inflammatory disorders involving neutrophil ${text{O}}_{{text{2}} cdot }^--$ production.

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