Tissue plasminogen activator and plasmin independently decrease human neutrophil activation.
Tissue-plasminogen activator (t-PA) and plasmin both decrease platelet aggregation, which may contribute to thrombolysis and tissue salvage. Since neutrophils may contribute to reperfusion injury, we examined the effects of t-PA and plasmin on human neutrophil function. t-PA (1 to 100 micrograms/ml) decreased f-MLP-induced chemotaxis and ionophore A23187-induced superoxide and LTB4 release in isolated neutrophils, and these effects were not blocked by the plasmin-inhibitor epsilon-aminocaproic acid (epsilon-ACA). On the other hand, plasmin (0.05 to 0.5 units/ml) also decreased these neutrophil functions but its effects were blocked in the presence of epsilon-ACA. Thus, while both t-PA and plasmin decrease neutrophil functions, effects of t-PA are independent of plasmin generation. Cumulative effects of t-PA and plasmin on neutrophil functions may relate to the overall efficacy of t-PA in thrombotic disorders.
Mehta
J L
JL
Department of Medicine, College of Medicine, University of Florida, Gainesville.
Mehta
P
P
Lawson
D L
DL
Herzbrun
L
L
D000001:Calcimycin / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D013481:Superoxides; D007975:Leukotriene B4; D000001:Calcimycin; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin