Activation of mouse peritoneal macrophages by monoclonal antibodies to Mac-1 (complement receptor type 3).
Several features of activation of mouse peritoneal macrophages were elicited by 1-2-d exposure to submicrogram concentrations of anti-Mac-1 (M1/70), a rat monoclonal antibody that reacts with the alpha chain of complement receptor type 3 (Mac-1). The changes induced included enhanced capacity to secrete H2O2 when triggered with PMA, decreased secretion of proteins, increased expression of Ia antigen and decreased phagocytosis of particles. These changes closely resembled those induced by rIFN-gamma in type, extent, and time course. The concentration of M1/70 IgG resulting in 50% of the maximal activation of macrophage H2O2-releasing capacity averaged 0.18 +/- 0.03 micrograms/ml. This activation was not blocked by anti-FcR mAb, and could be reproduced with M18/2, a mAb against beta chain of Mac-1, suggesting that a direct ligation of Mac-1 with mAb was responsible for the activation. Neither depletion of T cells nor addition of neutralizing Abs to IFN-gamma or TNF-alpha prevented M1/70-mediated macrophage activation. Moreover, F(ab')2 of M1/70, or plating of macrophages on C3bi-coated surfaces, inhibited the activation of macrophages by rIFN-gamma. These findings suggest that Mac-1 (CR3) may play an important role in macrophage activation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology*; D000954:Antigens, Surface / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology; D007700:Kinetics; D008262:Macrophage Activation; D016177:Macrophage-1 Antigen; D051379:Mice; D008813:Mice, Inbred ICR; D010587:Phagocytosis; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006023:Glycoproteins; D000949:Histocompatibility Antigens Class II; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D006861:Hydrogen Peroxide