Final decision: D. Lane, 5 April 2013
Acute-phase concentrations of soluble fibrinogen inhibit neutrophil adhesion under flow conditions in vitro through interactions with ICAM-1 and MAC-1 (CD11b/CD18)
Article first published online: 3 JUL 2013
© 2013 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 11, Issue 6, pages 1172–1182, June 2013
How to Cite
Acute-phase concentrations of soluble fibrinogen inhibit neutrophil adhesion under flow conditions in vitro through interactions with ICAM-1 and MAC-1 (CD11b/CD18). J Thromb Haemost 2013; 11: 1172–82., , , , , , .
Contributed equally to the study.
Manuscript handled by: W. Aird
- Issue published online: 3 JUL 2013
- Article first published online: 3 JUL 2013
- Accepted manuscript online: 13 APR 2013 09:28AM EST
- Manuscript Received: 28 SEP 2012
- systemic inflammatory response syndrome
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.
To study the effect of soluble fibrinogen in concentrations found in severe acute inflammation on leukocyte adhesion.
Isolated leukocytes and soluble fibrinogen were studied in various in vitro settings under static and under flow conditions.
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.
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.