title: Acute-phase concentrations of soluble fibrinogen inhibit neutrophil adhesion under flow conditions in vitro through interactions with ICAM-1 and MAC-1 (CD11b/CD18).
abstract: BACKGROUND
  Immobilized fibrinogen and fibrin facilitate leukocyte adhesion, as they are potent ligands for leukocyte MAC-1 (CD11b/CD18). However, fibrinogen in its soluble form also binds to MAC-1, albeit with low affinity. The level of soluble fibrinogen is increased during chronic and acute inflammation, but the function of this increase is unknown.
  
  
  OBJECTIVE
  To study the effect of soluble fibrinogen in concentrations found in severe acute inflammation on leukocyte adhesion.
  
  
  METHODS
  Isolated leukocytes and soluble fibrinogen were studied in various in vitro settings under static and under flow conditions.
  
  
  RESULTS
  Soluble fibrinogen functioned as a natural antagonist of neutrophil functions that are dependent on MAC-1, such as the respiratory burst induced by unopsonized zymosan and adhesion to ICAM-1 and heparin. In addition, soluble fibrinogen inhibited lymphocyte function-associated antigen 1-dependent lymphocyte binding to ICAM-1 through a direct interaction with ICAM-1. Soluble fibrinogen reduced MAC-1-dependent binding of interleukin-8-activated neutrophils to ICAM-1-expressing cells under flow conditions. Importantly soluble fibrinogen in acute-phase concentrations (4-10 mg mL(-1) ) dose-dependently reduced neutrophil firm adhesion to tumor necrosis factor-α-activated endothelium to 40% under flow conditions.
  
  
  CONCLUSIONS
  We propose a model in which the increased circulating concentrations of soluble fibrinogen found during the acute-phase response can act as a natural antagonist of leukocyte recruitment, and therefore might contribute to the resolution of inflammation.
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Pillay
authors.forename: V M
authors.initials: VM
authors.lastname: Kamp
authors.forename: M
authors.initials: M
authors.lastname: Pennings
authors.forename: E-J
authors.initials: EJ
authors.lastname: Oudijk
authors.forename: L P
authors.initials: LP
authors.lastname: Leenen
authors.forename: L H
authors.initials: LH
authors.lastname: Ulfman
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
mesh_terms: D000210:Acute-Phase Reaction / Q000378:metabolism*; D000818:Animals; D018821:CD18 Antigens / Q000737:chemistry*; D002118:Calcium / Q000737:chemistry; D002448:Cell Adhesion; D002465:Cell Movement; D003600:Cytosol / Q000378:metabolism; D004727:Endothelium / Q000473:pathology; D005340:Fibrinogen / Q000737:chemistry*; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry*; D008213:Lymphocyte Activation; D051379:Mice; D009504:Neutrophils / Q000166:cytology* / Q000276:immunology; D011485:Protein Binding; D016897:Respiratory Burst; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018821:CD18 Antigens; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002118:Calcium
keywords: endothelium; inflammation; leukocyte; migration; systemic inflammatory response syndrome