Fibrinogen counteracts the antiadhesive effect of fibrin-bound plasminogen by preventing its activation by adherent U937 monocytic cells

V. K. Lishko, I. S. Yermolenko, H. Owaynat, Tatiana Ugarova

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: Fibrinogen and plasminogen strongly reduce adhesion of leukocytes and platelets to fibrin clots, highlighting a possible role for these plasma proteins in surface-mediated control of thrombus growth and stability. In particular, adsorption of fibrinogen on fibrin clots renders their surfaces non-adhesive, while the conversion of surface-bound plasminogen to plasmin by transiently adherent blood cells results in degradation of a superficial fibrin layer, leading to cell detachment. Although the mechanisms whereby these proteins exert their antiadhesive effects are different, the outcome is the same: the formation of a mechanically unstable surface that does not allow firm cell attachment. Objectives: Since fibrin clots in circulation are exposed to both fibrinogen and plasminogen, their combined effect on adhesion of monocytic cells was examined. Methods: Fibrin gels were coated with plasminogen and its activation by adherent U937 monocytic cells in the presence of increasing concentrations of fibrinogen was examined by either measuring 125I-labeled fibrin degradation products or plasmin amidolytic activity. Results: Unexpectedly, the antiadhesive effects of two fibrin binding proteins were not additive; in fact, in the presence of fibrinogen, the effect of plasminogen was strongly reduced. An investigation of the underlying mechanism revealed that fibrinogen prevented activation of fibrin-bound plasminogen by cells. Confocal microscopy showed that fibrinogen accumulates in a thin superficial layer of a clot, where it exerts its blocking effect on activation of plasminogen. Conclusion: The results point to a complex interplay between the fibrinogen- and plasminogen-dependent antiadhesive systems, which may contribute to the mechanisms that control the adhesiveness of a fibrin shell on the surface of hemostatic thrombi.

Original languageEnglish (US)
Pages (from-to)1081-1090
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume10
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • Adhesion
  • Fibrinogen
  • Fibrinolysis
  • Plasminogen
  • Thrombus

ASJC Scopus subject areas

  • Hematology

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