Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u‐PA‐dependent mechanism

Many human thrombi lyse spontaneously without the administration of lytic drugs and cause no clinical symptoms. The mechanisms by which this occurs are incompletely understood. We found that model thrombi prepared from whole human blood in a Chandler loop also exhibited significant spontaneous lysis...

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Bibliographic Details
Published in:British journal of haematology 2001-04, Vol.113 (1), p.72-80
Main Authors: Moir, E., Booth, N. A., Bennett, B., Robbie, L. A.
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal - pharmacology
Biological and medical sciences
Blood coagulation. Blood cells
Cathepsin G
Cathepsins - physiology
Electrophoresis, Polyacrylamide Gel
Fundamental and applied biological sciences. Psychology
General aspects, investigation methods, hemostasis, fibrinolysis
Hematology
Humans
Immunohistochemistry
leucocytes
Models, Biological
Molecular and cellular biology
neutrophils
Neutrophils - physiology
Pancreatic Elastase - physiology
Receptors, Cell Surface - immunology
Receptors, Urokinase Plasminogen Activator
Serine Endopeptidases
Thrombosis - immunology
thrombus lysis
Tissue Plasminogen Activator - physiology
Urokinase-Type Plasminogen Activator - immunology
Urokinase-Type Plasminogen Activator - physiology
u‐PA
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Summary:Many human thrombi lyse spontaneously without the administration of lytic drugs and cause no clinical symptoms. The mechanisms by which this occurs are incompletely understood. We found that model thrombi prepared from whole human blood in a Chandler loop also exhibited significant spontaneous lysis. Lysis was inhibited by chemical protease inhibitors, consistent with proteolysis resulting primarily from serine proteases, with a small contribution from matrix metalloproteinases. Whole blood was fractionated into platelet‐rich plasma and cell populations. Significant spontaneous lysis was observed in platelet‐rich thrombi enriched with polymorphonuclear leucocytes (PMNs), whereas mononuclear cells (MCs) and erythrocytes did not contribute to lysis. Incorporation of antibodies to urokinase (u‐PA) and its receptor u‐PAR neutralized a large proportion of the activity. Incubation of plasma with PMNs generated free u‐PA activity, which was also detectable in model thrombi and in vivo human thrombi. Purified neutrophils, free of eosinophils, generated activity identical to PMNs. Smaller contributions to lysis by tissue‐type plasminogen activator (t‐PA), elastase and cathepsin G were also identified. These findings suggest a major role for circulating PMNs in endogenous thrombus lysis.
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.2001.02696.x