Polymorphonuclear leucocytes have two opposing roles in fibrinolysis

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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Polymorphonuclear leucocytes (PMN) are important in the resolution of human thrombi, with u-PA as a key player. We have shown that the u-PA activity of PMN depends on the presence of plasma; the study presented here provides an explanation for that requirement, Here we show that PMN degraded scu-PA and also tcu-PA, t-PA and plasmin, resulting in loss of fibrinolytic activity. Plasma protected against this degradation; alpha(1)-antitrypsin was identified as a protective factor. Purified human neutrophil elastase mirrored the effects of PMN, again neutralized by plasma inhibitors. These findings illustrate the dual role of PMN in the breakdown of thrombi, in that they contribute both u-PA, which lyses fibrin, and other proteases, including elastase, which can cleave Fibrin and plasminogen activators/plasmin. Similarly, plasma can potentiate fibrinolysis by neutralization of PMN elastase, in addition to direct inhibition of fibrinolytic proteases. Our previous studies show that PMN in thrombi are mostly pro-fibrinolytic, the antifibrinolytic role defined here may be important in other pathologies where fibrin persists.

Original languageEnglish
Pages (from-to)1006-1010
Number of pages4
JournalThrombosis and Haemostasis
Volume87
Issue number6
Publication statusPublished - 2002

Keywords

  • polymorphonuclear leucocytes
  • elastase
  • alpha(1)-antitrypsin
  • u-PA
  • PLASMINOGEN-ACTIVATOR
  • U-PA
  • ARTERIAL THROMBI
  • CLOT LYSIS
  • LEUKOCYTES
  • UROKINASE
  • ELASTASE
  • PROTEASES
  • GRANULOCYTES
  • MODULATION

Cite this

Polymorphonuclear leucocytes have two opposing roles in fibrinolysis. / Moir, E.; Robbie, L. A.; Booth, Nuala Ann; Bennett, B.

In: Thrombosis and Haemostasis, Vol. 87, No. 6, 2002, p. 1006-1010.

Research output: Contribution to journalArticle

Moir, E, Robbie, LA, Booth, NA & Bennett, B 2002, 'Polymorphonuclear leucocytes have two opposing roles in fibrinolysis', Thrombosis and Haemostasis, vol. 87, no. 6, pp. 1006-1010.
Moir, E. ; Robbie, L. A. ; Booth, Nuala Ann ; Bennett, B. / Polymorphonuclear leucocytes have two opposing roles in fibrinolysis. In: Thrombosis and Haemostasis. 2002 ; Vol. 87, No. 6. pp. 1006-1010.
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AU - Moir, E.

AU - Robbie, L. A.

AU - Booth, Nuala Ann

AU - Bennett, B.

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N2 - Polymorphonuclear leucocytes (PMN) are important in the resolution of human thrombi, with u-PA as a key player. We have shown that the u-PA activity of PMN depends on the presence of plasma; the study presented here provides an explanation for that requirement, Here we show that PMN degraded scu-PA and also tcu-PA, t-PA and plasmin, resulting in loss of fibrinolytic activity. Plasma protected against this degradation; alpha(1)-antitrypsin was identified as a protective factor. Purified human neutrophil elastase mirrored the effects of PMN, again neutralized by plasma inhibitors. These findings illustrate the dual role of PMN in the breakdown of thrombi, in that they contribute both u-PA, which lyses fibrin, and other proteases, including elastase, which can cleave Fibrin and plasminogen activators/plasmin. Similarly, plasma can potentiate fibrinolysis by neutralization of PMN elastase, in addition to direct inhibition of fibrinolytic proteases. Our previous studies show that PMN in thrombi are mostly pro-fibrinolytic, the antifibrinolytic role defined here may be important in other pathologies where fibrin persists.

AB - Polymorphonuclear leucocytes (PMN) are important in the resolution of human thrombi, with u-PA as a key player. We have shown that the u-PA activity of PMN depends on the presence of plasma; the study presented here provides an explanation for that requirement, Here we show that PMN degraded scu-PA and also tcu-PA, t-PA and plasmin, resulting in loss of fibrinolytic activity. Plasma protected against this degradation; alpha(1)-antitrypsin was identified as a protective factor. Purified human neutrophil elastase mirrored the effects of PMN, again neutralized by plasma inhibitors. These findings illustrate the dual role of PMN in the breakdown of thrombi, in that they contribute both u-PA, which lyses fibrin, and other proteases, including elastase, which can cleave Fibrin and plasminogen activators/plasmin. Similarly, plasma can potentiate fibrinolysis by neutralization of PMN elastase, in addition to direct inhibition of fibrinolytic proteases. Our previous studies show that PMN in thrombi are mostly pro-fibrinolytic, the antifibrinolytic role defined here may be important in other pathologies where fibrin persists.

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KW - ARTERIAL THROMBI

KW - CLOT LYSIS

KW - LEUKOCYTES

KW - UROKINASE

KW - ELASTASE

KW - PROTEASES

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KW - MODULATION

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JO - Thrombosis and Haemostasis

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