A Possible Self‐Regulating Mechanism Mediated by C3b‐Acceptor‐Bound C3b Generated by Stimulated Macrophages

Macrophages have been shown to produce C3 and to hear Fc receptors (FcR). and besides The various C3 receptors, they possess C3b acceptors (C3bA) as well as surface proteases capable of cleaving C3. Using the immune adherence method, we demonstrated that the amount of covalently fixed (i.e., C3bA‐bound) C3h is markedly increased upon cell stimulation by phorbol myristate acetate or aggregated IgG. even in the absence of C3. The enhancement of nascent C3b (C3bx) binding to C3bA on these cells could be reversed by inhibiting the process at different stages, using either cycloheximide. phenyl‐methyl‐sulphonyl‐fluoride, salycil hydroxamic acid, or methylamine. On the basis of our present results and earlier results, we propose a self‐regulatory mechanism by which activated. C3‐producing macrophages cleave C3 by their surface proteases. C3bx generated in this way fixes covalently to C3bA of the producer cells, resulting in the inhibition of FcR on these cells.

[1]  M. Dierich,et al.  C3 Cleaved by Membrane Proteases Binds to C3b Acceptors Expressed on Concanavalin A‐Stimulated Human Lymphocytes and Enhances Antibody‐Dependent Cellular Cytotoxicity , 1984, Scandinavian journal of immunology.

[2]  S. Gordon,et al.  Local opsonization by secreted macrophage complement components. Role of receptors for complement in uptake of zymosan , 1984, The Journal of experimental medicine.

[3]  G. Füst,et al.  C3b acceptors on human peripheral blood mononuclear cells; characterization and functional role. , 1983, Immunology.

[4]  J. Gergely,et al.  C3b acceptors on macrophages: inhibition of Fc gamma-receptor-mediated phagocytosis by acceptor-bound C3b. , 1983, Immunology letters.

[5]  J. Lambris,et al.  Identification of a C3bi-specific membrane complement receptor that is expressed on lymphocytes, monocytes, neutrophils, and erythrocytes , 1982, The Journal of experimental medicine.

[6]  H. Hartung,et al.  Quantitative studies of the secretion of complement component C3 by resident, elicited and activated macrophages. Comparison with C2, C4 and lysosomal enzyme release , 1982, European journal of immunology.

[7]  F. Rosen,et al.  The third component of complement: covalent attachment of a radioactive sugar to the labile binding site of C3 via the alternative pathway. , 1981, Journal of Immunology.

[8]  J. Lambris,et al.  Isolation of lymphocyte membrane complement receptor type two (the C3d receptor) and preparation of receptor-specific antibody. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. Fearon Identification of the membrane glycoprotein that is the C3b receptor of the human erythrocyte, polymorphonuclear leukocyte, B lymphocyte, and monocyte , 1980, The Journal of experimental medicine.

[10]  J. Ferluga,et al.  Production of the complement cleavage product, C3a, by activated macrophages and its tumorolytic effects. , 1978, Clinical and experimental immunology.

[11]  H. Chapman,et al.  Macrophage tumor killing: influence of the local environment. , 1977, Science.

[12]  J. Prahl,et al.  Third component of human complement: purification from plasma and physicochemical characterization. , 1976, Biochemistry.

[13]  S. Wahl,et al.  Role of a peptidase in phagocyte chemotaxis. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[14]  A. Allison,et al.  Ability of activated complement components to induce lysosomal enzyme release from macrophages , 1976, Nature.

[15]  H. Remold The enhancement of MIF activity by inhibition of macrophage associated esterases. , 1974, Journal of immunology.

[16]  S. J. Holt A New Principle for the Histochemical Localization of Hydrolytic Enzymes , 1952, Nature.