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

To cite this article: Pillay J, Kamp VM, Pennings M, Oudijk E-J, Leenen LP, Ulfman LH, Koenderman L. 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.Summary. 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. Objectives: 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 functionassociated 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 À1 ) dosedependently reduced neutrophil firm adhesion to tumor necrosis factor-a-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.

Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry

“…Studies have shown CD11b to be directly involved in cellular adhesion, however migration will only take place if CD18 subunit is present. CD11b is known to be expressed in many leukocytes subsets including monocytes, neutrophils, natural killer cells, and macrophages [26]. CD16 is glycosyl phosphatidyl inositol-anchored (GPI) protein that acts as a receptor for the Fc region of immunoglobulin gamma (Fc gamma RIII).…”

Role of Fibrinogen in the Attenuation of the Ischemic Reperfusion Injury and in Remote Ischemic Preconditioning

“…On the contrary to the proinflammatory effects of immobilized FB/ fibrin, sFB has the ability to inhibit lymphocytic antigen 1-dependent binding to ICAM-1 through a direct interaction with ICAM-1 [7], and to reduce IL8-activated neutrophils binding to ICAM-1-expressing cells, in addition to reducing the binding of neutrophils to TNFα-activated endothelium to 40%, under flow conditions [33].…”

Multiple Sclerosis Under Attack; Shehata’s Therapy

“…In addition, the interaction between FB and αM βII-integrin receptor results in the activation of Talin-1, which interacts with Rap-1 and is essential for adhesion, migration and phagocytosis activity of antigen-presenting cells and lymphocytes. [46] Although there is a strong evidence that fibrinogen plays an important pro-inflammatory role in the development of MS, this might be limited to the deposited FB (insoluble FB), which is out of doubt incorporated in the recruitment of lymphocytes and macrophages. Thus, the sequence of events in this regards might be simplified as disruption of the BBB → leakage of FB into CSF → perivascular deposition of FB → recruitment and chemotaxis of macrophages, T-and B-lymphocytes, which produce inflammatory cytokines and attack the myelin sheathes.…”

“…This hypothesis might be supported by the finding that the fibrinogen leakage into CSF was not reported during the remission, but coincides with the fulminant MS. [47] In contrast with the pro-inflammatory effects of immobilized FB/fibrin, sFB has the ability to inhibit lymphocytic antigen 1-dependent binding to the intracellular adhesion molecule 1 (ICAM-1) through a direct interaction with ICAM-1 [48] , and to reduce interleukin (IL) 8-activated neutrophils binding to ICAM-1-expressing cells, in addition to reducing the binding of neutrophils to TNFα-activated endothelium to 40%, under flow conditions. [46] Accordingly, blocking the pro-inflammatory functions of FB would ideally protect against its role in the recruitment of the inflammatory cells into CNS, which coincidence with disease progression and or exacerbation, without affecting its other vital functions, such as its role in the …”