TY - JOUR T1 - Histamine H<sub>4</sub> and H<sub>2</sub> Receptors Control Histamine-Induced Interleukin-16 Release from Human CD8<sup>+</sup> T Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 300 LP - 307 DO - 10.1124/jpet.102.036939 VL - 303 IS - 1 AU - Florian Gantner AU - Katsuya Sakai AU - Michael W. Tusche AU - William W. Cruikshank AU - David M. Center AU - Kevin B. Bacon Y1 - 2002/10/01 UR - http://jpet.aspetjournals.org/content/303/1/300.abstract N2 - Histamine is known to trigger the release of interleukin (IL)-16 from human CD8+ cells. However, the individual roles of the presently known histamine receptor subtypes (H1-H4) in this inflammatory response have not been fully characterized. Histamine stimulation of human CD8+ T lymphocytes purified from peripheral blood led to a 5- to 8-fold increase in the basal release of IL-16 within 24 h, and this increase was significantly blocked by the H2-selective antagonist, cimetidine, or by thioperamide, an antagonist of H3 and H4 receptors, respectively. The H1 antagonist pyrilamine showed limited effects. Agonists selective for H2 (dimaprit), H3/4 (R-(−)-α-methylhistamine), and H4 (clobenpropit) were capable of inducing the release of bioactive IL-16 because CD8+ cell supernatants induced CD4+ cell migration, which was abrogated by an anti-IL-16 antibody. Furthermore, preincubation of lymphocytes with pertussis toxin abolished IL-16 release triggered by activation of the Gi/o-coupled H4 receptor but not by the H2 receptor. Messenger RNA expression studies confirmed H4, H2, and H1 expression in human CD8+ lymphocytes, whereas H3 mRNA was completely absent. All leukocyte populations investigated expressed mRNA for H4, with highest levels found in eosinophils, dendritic cells, and tonsil B cells. H4 expression was also detected in human lung, trachea, and various cells of human lung origin, such as fibroblasts, bronchial smooth muscle cells, epithelial, and endothelial cells. Since many of those are known sources of IL-16, immune cell- and lung cell-expressed H4 receptors may have a general role in the control of this mediator of inflammatory disorders such as asthma. The American Society for Pharmacology and Experimental Therapeutics ER -