Evidence that exposure to fibrinogen or to antibodies directed against Mac-1 (CD11b/CD18; CR3) modulates human monocyte effector functions.
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.
Trezzini
C
C
Institute of Veterinary Virology, University of Berne, Switzerland.
Schüepp
B
B
Maly
F E
FE
Jungi
T W
TW
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004912:Erythrocytes / Q000276:immunology; D005340:Fibrinogen / Q000502:physiology*; D006801:Humans; D008163:Luminescent Measurements; D016177:Macrophage-1 Antigen / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism / Q000502:physiology*; D010101:Oxygen Consumption; D010587:Phagocytosis / Q000502:physiology; D011961:Receptors, Fc / Q000502:physiology
D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D005340:Fibrinogen