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Evidence that exposure to fibrinogen or to antibodies directed against Mac-1 (CD11b/CD18; CR3) modulates human
C Trezzini1, B Schüepp, F E Maly
1Institute of Veterinary Virology, University of Berne, Switzerland.
Abstract:
We have recently shown that the treatment of fibrinogen-coated monocytes (MO) with anti-fibrinogen as well as the exposure of MO to surface-bound fibrinogen (Fg) or to albumin haptenized with the Fg C-gamma-terminal pentadecapeptide, induces on oxidative burst. Using chemiluminescence (CL) for indicating an oxidative burst, and the ingestion of IgG-coated erythrocytes as a test of phagocytosis, we have now studied the impact of Fg on MO effector functions. MO that had been either pretreated with Fg and washed, or that were exposed to surface-adsorbed Fg, exhibited impaired Fc receptor-mediated phagocytosis. A similar impairment was observed when MO were pretreated with activating agents such as phorbol myristate acetate, n-formyl-methionyl-leucyl-phenylalanine (fMLP) or the calcium ionophore A23187. Moreover, following exposure to Fg or IgG, MO exhibited a reduced oxidative burst upon stimulation with a variety of agents. Similarly, MO pretreated or coincubated with anti-Mac-1 exhibited a reduced oxidative burst upon stimulation. Our results raise the possibility that inflammatory mononuclear phagocytes experience a functional modulation upon encountering fibrin by interacting with specific receptors for fibrin(ogen). This type of modulation is analogous to effects induced by the triggering of Fc gamma receptors. MO showed a decreased oxidative burst when either pretreated or coincubated with anti-Mac-1 antibodies, whereas antibodies directed against other MO surface constituents had no, or a weak effect only. This is compatible with the suggestion that Mac-1 acts as a fibrin (ogen) receptor.
Insights
Fibrinogen (Fg) exposure impairs monocyte (MO) functions like phagocytosis and oxidative burst. This suggests fibrinogen binding to Mac-1 receptors modulates inflammatory responses in mononuclear phagocytes.
Area of Science:
- Immunology
- Cell Biology
- Hematology
Background:
- Mononuclear phagocytes (MO) play a crucial role in immune responses.
- Fibrinogen (Fg) is a key protein in coagulation and inflammation.
- Previous studies indicated Fg can induce an oxidative burst in MO.
Purpose of the Study:
- To investigate the impact of fibrinogen (Fg) on effector functions of monocytes (MO).
- To explore the role of Mac-1 receptor in fibrinogen-mediated modulation of MO functions.
Main Methods:
- Chemiluminescence (CL) was used to measure oxidative burst.
- Phagocytosis was assessed using IgG-coated erythrocytes.
- Monocytes were treated with fibrinogen, activating agents, or anti-Mac-1 antibodies.
Main Results:
- Fibrinogen exposure impaired Fc receptor-mediated phagocytosis in MO.
- Fg or IgG exposure reduced the oxidative burst response of MO to various stimuli.
- Anti-Mac-1 antibodies, but not others, reduced the oxidative burst, suggesting Mac-1 is a fibrinogen receptor.
Conclusions:
- Fibrinogen binding to monocytes can modulate their effector functions, including phagocytosis and oxidative burst.
- The Mac-1 receptor appears to be involved in mediating these fibrinogen-induced effects.
- These findings suggest a mechanism for how fibrinogen influences inflammatory mononuclear phagocytes.