Acute-phase concentrations of soluble fibrinogen inhibit neutrophil adhesion under flow conditions invitro through interactions with ICAM-1 and MAC-1 (CD11b/CD18)

作者：Pillay J; Kamp V M; Pennings M; Oudijk E J; Leenen L P; Ulfman L H; Koenderman L^*

来源：Journal of Thrombosis and Haemostasis, 2013, 11(6): 1172-1182.

DOI：10.1111/jth.12250

• endothelium
• inflammation
• leukocyte
• migration
• systemic inflammatory response syndrome

BackgroundImmobilized 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.
ObjectivesTo study the effect of soluble fibrinogen in concentrations found in severe acute inflammation on leukocyte adhesion.
MethodsIsolated leukocytes and soluble fibrinogen were studied in various invitro settings under static and under flow conditions.
ResultsSoluble 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 antigen1-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 (4-10mgmL(-1)) dose-dependently reduced neutrophil firm adhesion to tumor necrosis factor--activated endothelium to 40% under flow conditions.
ConclusionsWe 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.

• 出版日期2013-6