title: Histamine improves antigen uptake and cross-presentation by dendritic cells.
abstract: Previous studies have shown that histamine is able to modulate the function of dendritic cells (DCs). Histamine seems to be required for the normal differentiation of DCs. Moreover, it is capable of stimulating the chemotaxis of immature DCs and of promoting the differentiation of T CD4+ cells into a Th2 profile. In this study, we analyzed whether histamine was able to modulate endocytosis and cross-presentation mediated by immature DCs. Our results show that both functions are stimulated by histamine. Endocytosis of soluble HRP and FITC-OVA and cross-presentation of soluble OVA were markedly increased by histamine. Interestingly, stimulation of endocytosis and cross-presentation appeared to be mediated through different histamine receptors. In fact, the enhancement of endocytosis was prevented by the histamine2 receptor (H2R) antagonist cimetidine, whereas the stimulation of cross-presentation was prevented by the H3R/H4R antagonist thioperamide. Of note, contrasting with the observations made with soluble Ags, we found that histamine did not increase either the uptake of OVA-attached to latex beads, or the cross-presentation of OVA immobilized on latex beads. This suggests that the ability of histamine to increase endocytosis and cross-presentation is dependent on the Ag form and/or the mechanisms through which the Ag is internalized by DCs. Our results support that histamine may favor cross-presentation of soluble allergens by DCs enabling the activation of allergen-specific T CD8+ cells, which appears to play an important role in the development of allergic responses in the airway.
authors.affiliation: Institute of Hematologic Research, National Academy of Medicine and National Reference Center for AIDS, Department of Microbiology, Buenos Aires University School of Medicine, Buenos Aires, Argentina.
authors.forename: Maria Marta
authors.initials: MM
authors.lastname: Amaral
authors.forename: Carlos
authors.initials: C
authors.lastname: Davio
authors.forename: Ana
authors.initials: A
authors.lastname: Ceballos
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salamone
authors.forename: Cristian
authors.initials: C
authors.lastname: Cañones
authors.forename: Jorge
authors.initials: J
authors.lastname: Geffner
authors.forename: Mónica
authors.initials: M
authors.lastname: Vermeulen
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology; D005260:Female; D006632:Histamine / Q000096:biosynthesis / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006967:Hypersensitivity / Q000276:immunology / Q000378:metabolism; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011969:Receptors, Histamine H1 / Q000096:biosynthesis; D011970:Receptors, Histamine H2 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism