title: Histamine h(4) and h(2) receptors control histamine-induced interleukin-16 release from human CD8(+) T cells.
abstract: 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 (H(1)-H(4)) 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 H(2)-selective antagonist, cimetidine, or by thioperamide, an antagonist of H(3) and H(4) receptors, respectively. The H(1) antagonist pyrilamine showed limited effects. Agonists selective for H(2) (dimaprit), H(3/4) (R-(-)-alpha-methylhistamine), and H(4) (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 G(i/o)-coupled H(4) receptor but not by the H(2) receptor. Messenger RNA expression studies confirmed H(4), H(2), and H(1) expression in human CD8(+) lymphocytes, whereas H(3) mRNA was completely absent. All leukocyte populations investigated expressed mRNA for H(4), with highest levels found in eosinophils, dendritic cells, and tonsil B cells. H(4) 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 H(4) receptors may have a general role in the control of this mediator of inflammatory disorders such as asthma.
authors.affiliation: Bayer Yakuhin, Ltd., Research Center Kyoto, Therapeutic Research Area Asthma, Japan. florian.gantner.fg@bayer.co.jp
authors.forename: Florian
authors.initials: F
authors.lastname: Gantner
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sakai
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tusche
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.forename: David M
authors.initials: DM
authors.lastname: Center
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Bacon
mesh_terms: D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002927:Cimetidine / Q000494:pharmacology; D017931:DNA Primers; D017259:Dimaprit / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D019410:Interleukin-16 / Q000378:metabolism*; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011738:Pyrilamine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000074040:Receptors, Histamine H4
chemical_list: D017931:DNA Primers; C418607:HRH4 protein, human; D019410:Interleukin-16; D008761:Methylhistamines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D000074040:Receptors, Histamine H4; C069357:alpha-methylhistamine; D002927:Cimetidine; D006632:Histamine; D011738:Pyrilamine; D017259:Dimaprit