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Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u‐PA‐dependent mechanism
Author(s) -
Moir E.,
Booth N. A.,
Bennett B.,
Robbie L. A.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02696.x
Subject(s) - cathepsin g , lysis , proteases , platelet lysate , plasminogen activator , microbiology and biotechnology , proteolysis , platelet , serine protease , whole blood , elastase , cathepsin , biology , lytic cycle , chemistry , immunology , protease , biochemistry , enzyme , endocrinology , virus
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.