title: The efficient bovine insulin presentation capacity of bone marrow-derived macrophages activated by granulocyte-macrophage colony-stimulating factor correlates with a high level of intracellular reducing thiols.
abstract: Bone marrow-derived macrophages (BMM phi) were shown before to function as antigen-presenting cells. We show here, that the antigen presentation capacity of BMM phi depends on the nature of the antigen and is differently regulated by the lymphokines interferon-gamma (IFN-gamma) and granulocyte/macrophage-colony-stimulating factor (GM-CSF). When bovine insulin (BI) was employed as antigen, only BMM phi treated with GM-CSF (GM-CSF-M phi) were efficient presenters, but when presentation of the antigens ovalbumin and conalbumin was tested, IFN-gamma-pulsed BMM phi (IFN-gamma-M phi) proved superior to GM-CSF-M phi. The lack of efficient BI presentation function of IFN-gamma-M phi was only obvious, when native BI was used as antigen. Preprocessed BI was presented by IFN-gamma-M phi with drastically higher efficiency than by GM-CSF-M phi. Because processing of insulin depends on reduction of disulfide bonds, we analyzed the content of intracellular reducing thiols within IFN-gamma-M phi, GM-CSF-M phi, and untreated BMM phi. Only after stimulation with GM-CSF did the amount of reduced glutathione and cysteine strongly increase, while IFN-gamma did not efficiently augment the intracellular content of both thiols. These findings suggest that the lymphokines IFN-gamma and GM-CSF differently interfere with the processing capacity of BMM phi by differently regulating the intracellular concentration of the thiols reduced glutathione and cysteine. A high level of these thiols induced by GM-CSF correlates with a prominent capacity to present the antigen bovine insulin.
authors.affiliation: Institut für Immunologie, Johannes Gutenberg Universität, Mainz, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Frosch
authors.forename: U
authors.initials: U
authors.lastname: Bonifas
authors.forename: H P
authors.initials: HP
authors.lastname: Eck
authors.forename: M
authors.initials: M
authors.lastname: Bockstette
authors.forename: W
authors.initials: W
authors.lastname: Droege
authors.forename: E
authors.initials: E
authors.lastname: Rüde
authors.forename: A B
authors.initials: AB
authors.lastname: Reske-Kunz
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001854:Bone Marrow Cells; D002417:Cattle; D003545:Cysteine / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007328:Insulin / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D013438:Sulfhydryl Compounds / Q000378:metabolism*
chemical_list: D007328:Insulin; D013438:Sulfhydryl Compounds; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005978:Glutathione; D003545:Cysteine