RESUMO
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.
Assuntos
Apresentação Cruzada/imunologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Histamina/fisiologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Diferenciação Celular/imunologia , Células Cultivadas , Endocitose/fisiologia , Feminino , Histamina/biossíntese , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Imunofenotipagem , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Receptores Histamínicos H1/biossíntese , Receptores Histamínicos H2/biossíntese , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Two populations of histaminergic H1 receptors with distinct high and low affinity binding sites were characterized by the specific H1 receptor antagonist [3H]mepyramine in autoimmune myocardium. No saturable binding of the radiolabelled H1 antagonist was observed in normal myocardium. Reaction of autoimmune myocardium with specific H1 agonist (2-thiazolylethylamine (ThEA)) triggered positive inotropy and negative chronotropy, which were inhibited by mepyramine. Inhibitors of phospholipase C and protein kinase C attenuated both the inotropic and chronotropic effects of ThEA, suggesting the participation of phosphoinositide hydrolysis in this phenomenon. The latter was verified by measurement of polyphosphoinositide hydrolysis in autoimmune myocardium following the reaction of ThEA with histaminergic H1 receptors. We conclude that functional H1 histaminergic receptors could involve a distinctive mechanism operating in autoimmune myocardium as a result of cardiac antigen immunization.