Histamine improves antigen uptake and cross-presentation by dendritic cells.

AMARAL M; DAVIO CARLOS; CEBALLOS A; SALAMONE G; CANONES C

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Lugar: Bethesda; Año: 2007 vol. 179 p. 3425 - 3433

0022-1767

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. The Journal of Immunology, 2007, 179: 3425–3433.