title: Characterization of immunosuppressive functions of murine peritoneal macrophages induced with various agents.
abstract: Murine peritoneal macrophages (M phi s), induced with stimuli such as thioglycollate, zymosan A, OK-432, bacille Calmette-Guérin (BCG), or live Mycobacterium intracellulare, showed varying levels of inhibitory activity against the concanavalin A (Con A) blastogenic response of splenic T cells. All test M phi s significantly inhibited the interleukin 2 (IL-2)-producing ability of T cells but this inhibition was not enough to explain the observed reduction in T cell Con A mitogenesis. In contrast, they markedly inhibited IL-2-reactive T cell generation, and the inhibition was sufficient to cause the reduction in T cell mitogenesis. A general relationship was observed between immunosuppressive activity of a given M phi and its active oxygen-producing ability (measured in terms of chemiluminescence) in response to phorbol myristate acetate triggering (r = .84, P less than .005). However, the suppressor activity of test M phi s was not reduced by superoxide dismutase and catalase, indicating that active oxygen radicals themselves did not mediate the expression of the immunosuppressive activity of these M phi s. On the other ahnd, indomethacin (an inhibitor of prostaglandin synthesis) caused a partial reduction in their immunosuppressive activity. The suppressor activity of M phi s induced with intraperitoneal injection of recombinant interferon gamma (IFN-gamma) was markedly reduced in the presence of myoglobin, a scavenger for nitric oxide radical (NO.). Tumor necrosis factor alpha (TNF alpha) failed to affect Con A mitogenesis of splenic T cells, even in combination with IFN-gamma. On the other hand, unsaturated long-chain fatty acids including oleic, linoleic, linolenic, and arachidonic acids markedly reduced the T cell function. These findings suggest some important roles of prostaglandins, NO., and long-chain unsaturated fatty acids as mediators of the expression of immunosuppressive function of the peritoneal M phi s.
authors.affiliation: Department of Microbiology and Immunology, Shimane Medical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tomioka
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000502:physiology; D005609:Free Radicals; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D007213:Indomethacin / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D008938:Mitosis / Q000187:drug effects; D009162:Mycobacterium avium / Q000502:physiology; D009163:Mycobacterium bovis / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology*; D010844:Picibanil / Q000494:pharmacology*; D011453:Prostaglandins / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D013864:Thioglycolates / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology*
chemical_list: D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D007166:Immunosuppressive Agents; D011453:Prostaglandins; D013864:Thioglycolates; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D009569:Nitric Oxide; D010844:Picibanil; D007371:Interferon-gamma; D015054:Zymosan; D010100:Oxygen; D007213:Indomethacin