Modulation of dendritic cell apoptosis and CD8+ cytotoxicity by histamine: role of Protein Kinase C

JULIETA ALCAIN; PODAZZA ENRIQUE; GORI SOLEDAD; GABRIELA SALAMONE; VERMEULEN, MÓNICA

Mediators of Inflammation

Hindawi

Lugar: London; Año: 2017 vol. 2017 p. 1 - 12

Dendritic cells (DC) areable to present extracellular antigens associatedwith the molecules of the major histocompatibility complex class I. Ina previous work, we demonstrated that the histamine (HIS),acting through H1/H4 receptors, increases thecross-presentation of soluble ovalbuminby murine DCand can to enhance the recruitment of specific CD8+ T lymphocytesduring the development of chronic inflammatory responses. Here, we studied in more depth the mechanisms underlying thisenhancement. We showed that thecytotoxicity of specific CD8+ lymphocytes isincreased in HIS-treated DC and it is lost by inhibition of vacuolar-ATPase that prevents endosomeacidification. It is known that HIS acts through G-protein coupledreceptors. The H1/H4 receptors are associated with a Gq subunit,which involves PKC signaling, a pathway related to the apoptotic process. Interestingly, wedemonstrated for the first time that HIS prevents DC apoptosis induced by heat-shockthrough the inhibition of caspase-3, a mechanism dependent on PKC activation,since it is reversed by its inhibition. By contrast, cytolytic activity of Tlymphocytes induced by HIS-stimulated DC was independent of PKC pathway.