TY - JOUR
T1 - Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia
AU - Renckens, Rosemarijn
AU - Weijer, Sebastiaan
AU - de Vos, Alex F.
AU - Pater, Jennie M.
AU - Meijers, Joost C.
AU - Hack, C. Erik
AU - Levi, Marcel
AU - van der Poll, Tom
PY - 2004
Y1 - 2004
N2 - Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n = 8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-alpha2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P <0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release. Conclusion - These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia
AB - Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n = 8), a plasmin activation inhibitor, or placebo (n = 8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-alpha2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P <0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-α1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release. Conclusion - These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia
U2 - https://doi.org/10.1161/01.ATV.0000118280.95422.48
DO - https://doi.org/10.1161/01.ATV.0000118280.95422.48
M3 - Article
C2 - 14739127
SN - 1079-5642
VL - 24
SP - 483
EP - 488
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 3
ER -