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The Journal of Immunology, 2007, 179, 3425 -3433
Copyright © 2007 by The American Association of Immunologists, Inc.

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Histamine Improves Antigen Uptake and Cross-Presentation by Dendritic Cells1

Maria Marta Amaral*, Carlos Davio{dagger}, Ana Ceballos*, Gabriela Salamone*, Cristian Cañones*, Jorge Geffner* and Mónica Vermeulen2,*

* 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; and {dagger} Laboratory of Radioisotopes, Buenos Aires University School of Pharmacology and Biochemestry, Buenos Aires, Argentina

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 costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the Consejo Nacional de Investigaciones Científicas y Técnicas and Agencia Nacional de Promoción Científica y Tecnológica, Argentina.

2 Address correspondence and reprint requests to Dr. Mónica Vermeulen, Departamento de Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina. E-mail address: mvermeulen{at}hematologia.anm.edu.ar

3 Abbreviations used in this paper: DC, dendritic cell; ER, endoplasmic reticulum; HR, histamine receptor; MFI, mean fluorescence intensity.







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