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 Citations (Scopus)

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 2012

Fingerprint

U937 Cells
Plasminogen
Fibrin
Fibrinogen
Fibrinolysin
Thrombosis
Fibrin Fibrinogen Degradation Products
Adhesiveness
Hemostatics
Cell Adhesion
Confocal Microscopy
Adsorption
Blood Proteins
Blood Cells
Carrier Proteins
Leukocytes
Blood Platelets
Gels
Growth

Keywords

  • Adhesion
  • Fibrinogen
  • Fibrinolysis
  • Plasminogen
  • Thrombus

ASJC Scopus subject areas

  • Hematology

Cite this

Fibrinogen counteracts the antiadhesive effect of fibrin-bound plasminogen by preventing its activation by adherent U937 monocytic cells. / Lishko, V. K.; Yermolenko, I. S.; Owaynat, H.; Ugarova, Tatiana.

In: Journal of Thrombosis and Haemostasis, Vol. 10, No. 6, 06.2012, p. 1081-1090.

Research output: Contribution to journalArticle

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