title: Histamine synthesis is required for granule maturation in murine mast cells.
abstract: Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc(-/-) mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc(-/-) peritoneal mast cells. Impaired granule maturation was also found in Hdc(-/-) BM-derived cultured mast cells when they were cocultured with fibroblasts in the presence of c-kit ligand. Exogenous application of histamine and several H4 receptor agonists restored the granule maturation of Hdc(-/-) cultured mast cells. However, the maturation of granules was largely normal in Hrh4(-/-) peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter-2, did not affect granule maturation. In vivo experiments with mast cell deficient Kit(W) /Kit(W-v) mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator.
authors.affiliation: Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakazawa
authors.forename: Mariko
authors.initials: M
authors.lastname: Sakanaka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Furuta
authors.forename: Mayuko
authors.initials: M
authors.lastname: Natsuhara
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Takano
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okuno
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thurmond
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Hirasawa
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ichikawa
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D015550:Cell Degranulation; D002478:Cells, Cultured; D053818:Chymases / Q000378:metabolism; D018920:Coculture Techniques; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000276:immunology*; D006632:Histamine / Q000096:biosynthesis*; D006640:Histidine Decarboxylase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011968:Receptors, Histamine / Q000378:metabolism; D000074040:Receptors, Histamine H4; D022142:Secretory Vesicles / Q000378:metabolism*; D053802:Tryptases / Q000378:metabolism
chemical_list: C498829:Hrh4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D006632:Histamine; D053818:Chymases; D053802:Tryptases; D006640:Histidine Decarboxylase
keywords: Cell differentiation; Histamine; Inflammation; Mast cell