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Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u-PA-dependent mechanism by E. Moir; N. A. Booth; B. Bennett; L. A. Robbie is a Medicine article available to read on EtoBox.

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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 a

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Author

E. Moir; N. A. Booth; B. Bennett; L. A. Robbie

Publisher

John Wiley and Sons; Wiley (Blackwell Publishing); Blackwell Publishing Inc.; Wiley (ISSN 0007-1048)

Published

2001

Language

EN

Field

Medicine (Health Sciences)