Histamine-dendritic cell interacion: role of PKC

ALCAIN J.; FUENTES F.; GORI S.; BORGE, M.; SALAMONE G; VERMEULEN M

Congreso; IV Congreso de la Latin American Society for Immunodeficiencies (LASID); XIII Reunión de la Sociedad Argentina de Inmunología (SAI), y II Reunión del Congreso Franco-Argentino de Inmunología (FAIC); 2015

Background: dendritic cells (DCs) are able to presentextracellular antigens associated with the molecules of the majorhistocompatibility complex class I (CMHI), which leads toactivation of CD8+ T cells. Previously, we demonstrated thathistamine (HIS) improves cross presentation of ovalbumin (OVA)by murine CDs, an effect that is dependent of the V-ATPase sinceit was inhibited in the presence of bafilomycin. The HIS actsthrough G-protein coupled receptors. The H1 receptor isassociated with the Gq subunit, which involves PKC signaling.This pathway is related to the apoptotic process. Objective: Giventhis background, here we studied the modulation by the HIS ofDCs apoptosis and the mechanisms involved. Materials andMethods: The assays were performed using DCs differentiatedfrom bone marrow precursors of C57BL/6j mice, in the presenceof recombinant granulocyte-macrophage colony stimulating factor(GM-CSF). DCs were exposed to HIS (0.1µM) and the PKCinhibitor (Go-6983; 1nM). Extracts for Western blot analysis wereperformed after 10 min of stimulation with different treatments.Apoptotic damage was induced by heat shock and apoptosis wasevaluated 24 hours with Annexin-V+ propidium iodide. Results:HIS activates PKC pathway and decreases activation ofprocaspase 3, as seen by Western blot technique. Likewise, it alsoprotects DCs apoptosis after heat shock (DCs 27%, HIS 14.20%),which appears to be partially reversed by inhibition of PKC (HISinhib 17.89%). Conclusion: Our results demonstrate that theinteraction with HIS activates the PKC signaling pathway and thatthis would protect DCs from entering apoptosis.