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

E. Moir, Nuala Ann Booth, L. A. Robbie, B. Bennett

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)72-80
Number of pages8
JournalBritish Journal of Haematology
Volume113
Issue number1
DOIs
Publication statusPublished - 2001

Keywords

  • u-PA
  • leucocytes
  • thrombus lysis
  • neutrophils
  • TISSUE-PLASMINOGEN-ACTIVATOR
  • SOLUBLE UROKINASE RECEPTOR
  • ELASTASE-SPECIFIC INHIBITOR
  • LEUKOCYTE PROTEASES
  • ARTERIAL THROMBI
  • IN-VIVO
  • BINDING
  • CELLS
  • SYSTEM
  • PLASMA

Cite this

Polymorphonuclear leucocytes mediate endogenous thrombus lysis via a u-PA-dependent mechanism. / Moir, E.; Booth, Nuala Ann; Robbie, L. A.; Bennett, B.

In: British Journal of Haematology, Vol. 113, No. 1, 2001, p. 72-80.

Research output: Contribution to journalArticle

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AB - 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.

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