title: Fibrinogen counteracts the antiadhesive effect of fibrin-bound plasminogen by preventing its activation by adherent U937 monocytic cells.
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.
  
  
  OBJECTIVE
  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 (125) I-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Lishko
authors.forename: I S
authors.initials: IS
authors.lastname: Yermolenko
authors.forename: H
authors.initials: H
authors.lastname: Owaynat
authors.forename: T P
authors.initials: TP
authors.lastname: Ugarova
mesh_terms: D000327:Adsorption; D001665:Binding Sites; D002448:Cell Adhesion; D004789:Enzyme Activation; D005337:Fibrin / Q000378:metabolism*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005782:Gels; D006487:Hemostasis; D006801:Humans; D018613:Microscopy, Confocal; D009000:Monocytes / Q000201:enzymology*; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D020298:U937 Cells
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D005782:Gels; D005337:Fibrin; D005340:Fibrinogen; D010958:Plasminogen; D005341:Fibrinolysin