title: Lactoferrin acts on I-A and I-E/C antigen+ subpopulations of mouse peritoneal macrophages in the absence of T lymphocytes and other cell types to inhibit production of granulocyte-macrophage colony stimulatory factors in vitro.
abstract: The relationship between Ia antigens on mouse resident peritoneal macrophages and the ability of lactoferrin (LF) to inhibit the production of granulocyte-macrophage colony stimulatory factors (GM-CSF) from these cells was investigated. Detection of the suppressive influence of LF on release of GM-CSF from greater than or equal to 10(5) macrophages/ml/plate required that the conditioned media being assessed for GM-CSF be prepared in the presence of indomethacin and/or be preincubated with anti-ferritin antiserum to respectively stop production of E-type prostaglandins and to remove acidic isoferritin-inhibitory activities that can mask the effects of LF. Treatment of mouse macrophages with monoclonal antibodies to the I-A and I-E/C subregions of Ia antigens in a complement C-dependent cytotoxicity assay killed less than 15% of the cells, but removed all Ia antigen+ macrophages and reduced GM-CSF production by approximately 50%. LF decreased GM-CSF production by untreated macrophages by approximately 50%, but had no effect on macrophages insensitive to treatment with anti-Ia plus C. Macrophages left at 37 degrees C for 5 and 24 hr were not killed by treatment with monoclonal anti-Ia plus C and GM-CSF production by these macrophages was not suppressed by LF. Treatment of macrophages with monoclonal anti-H-2K or anti-Mac-1 plus C reduced GM-CSF production greater than 95%. Anti-I-A, -I-E/C, -H-2K, or -Mac-1, in the absence of C, had no effect on viability of macrophages or on production of GM-CSF, but anti-I-A and -I-E/C each blocked the inhibitory action of LF. Lower concentrations of these antibodies could block the action of LF when anti-I-A and anti-I-E/C were mixed together better than when they were each used separately. The removal of Thy-1.2+ cells from unseparated or adherent peritoneal cells resulted in populations of cells that were up to 100% positive for nonspecific esterase, and did not influence GM-CSF production from these cells, the reduction of GM-CSF from these cells by LF, or the reduction of GM-CSF by the removal of Ia antigen+ cells. The results were similar whether or not T cells were removed from the assay marrow by treatment with antibodies Ly-1.1, Ly-2.2, and Qa4 plus C.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000918:Antibody Specificity; D000954:Antigens, Surface / Q000276:immunology; D001202:Ascitic Fluid / Q000276:immunology; D001667:Binding, Competitive; D003115:Colony-Stimulating Factors / Q000096:biosynthesis* / Q000502:physiology; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007781:Lactoferrin / Q000494:pharmacology*; D007782:Lactoglobulins / Q000494:pharmacology*; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013601:T-Lymphocytes / Q000276:immunology; D018800:Thy-1 Antigens
chemical_list: D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D003115:Colony-Stimulating Factors; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D007782:Lactoglobulins; D016177:Macrophage-1 Antigen; D018800:Thy-1 Antigens; D007781:Lactoferrin