Effects of histamine on lymphocytes

Abstract

Histamine originally identified in 1900s is an important mediator of allergic disease, asthma and inflammation. Histamine has modulatory effects on different subpopulations of lymphoid cells. The pharmacologic effects of histamine are mediated through four types of membrane histamine receptors, H1R, H2R, H3R and H4R, which are all heptahelical G-protein-coupled receptors. Histamine receptors possess all structural features of G-protein-coupled receptors, including seven putative transmembrane domain, amino terminal glycosylation sites, and phosphorylation sites for protein kinase A and protein kinase C. Stimulation of H1R and H2R activates Gq and Gs respectively, whereas both H3R and H4R are coupled to Gi/o. Histamine affects a number of immune processes including regulation of T cells, antibody isotopes, antigen presenting cells and peripheral T cell tolerance. The conventional wisdom regarding the effects of histamine on Th1/Th2 subsets is that it shifts responses from Th1 to Th2 subsets resulting in allergic and asthmatic disease. While expression of H2 receptors on T cells has been well characterized; there is not a consensus on the function and expression of H1 receptors in the regulation of T cells. It has been suggested that Th1 cells may show a dominant expression of H1R and Th2 cells may show increased H2R. The effects of histamine on cytokine release and expression by T cells have been well established. Histamine suppresses the expression of Th1 cytokines and stimulates the secretion of Th2 cytokines via H2R. The recently discovered H4 receptors have drawn considerable interest pertaining to their effects on the regulation of immune response and inflammation. H4 receptor activates dendritic cells, regulates chemotaxis and migration of mast cells and eosinophils, and modulates cytokine release from T cells and dendritic cells. Histamine also regulates cytokine-dependent signal transduction pathways including JAK-STAT pathway. This chapter provides an overview of recent developments in understanding the role of histamine and its receptors in regulating the function of immune effector cells involved in allergic disease and asthma. © Springer Science+Business Media B.V. 2010.