Volume 77, Issue 1 pp. 16-24
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Evidence that exposure to fibrinogen or to antibodies directed against Mac-1 (CD11b/CD18; CR3) modulates human monocyte effector functions

C. Trezzini

C. Trezzini

Institutes of Veterinary Virology, Switzerland

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B. Schuuepp

B. Schuuepp

Institutes of Veterinary Virology, Switzerland

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F. E. Maly

F. E. Maly

Clinical Immunology, University of Berne, Berne, Switzerland

Institutes of Veterinary Virology, Switzerland

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T. W. Jungi

Corresponding Author

T. W. Jungi

Institutes of Veterinary Virology, Switzerland

Dr T. W. Jungi, Institute of Veterinary Virology, Langgass-Str. 122, CH-3012 Berne, Switzerland.Search for more papers by this author
First published: January 1991
Citations: 28

This work was supported by grants from the Swiss National Science Fund (T.W.J, and F.E.M.), from the Central Laboratory of the Swiss Red Cross Blood Transfusion Service (T.W.J.). and from the Arbeitsgemeinschaft für Osteosynthese (T.W.J.). The generous gift of monoclonal antibodies by Ortho Pharmaceutical, Raritan, N.J. (Dr P. Rao) and Dr K. Blaser. Swiss Institute of Asthma and Allergy Research, Davos, and the excellent technical assistance by Mrs M. BrčicA and H. Pfister is gratefully acknowledged.

Abstract

Summary. 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 an 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 Fcγ receptors. MO showed a decreased oxidative burst when either pretreated or coincubated with anti-Mac-1 antibodies, whereas antibodies directed against other MO surface constitutents had no, or a weak effect only. This is compatible with the suggestion that Mac-1 acts as a fibrin(ogen) receptor.

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