Mice lacking histidine decarboxylase exhibit abnormal mast cells

Ohtsu, Hiroshi; Tanaka, Satoshi; Terada, Tadashi; Hori, Yoshio; Makabe-Kobayashi, Yoko; Pejler, Gunnar; Tchougounova, Elena; Hellman, Lars; Gertsenstein, Marina; Hirasawa, Noriyasu; Sakurai, Eiko; Buzás, Edit I.; Kovács, P.; Csaba, G.; Kittel, Ágnes; Okada, M; Hara, Masahiro; Mar, Lynn; Numayama-Tsuruta, Keiko; Ishigaki-Suzuki, Satsuki; Ohuchi, Kazuo; Ichikawa, Atsushi; Falus, András; Watanabe, Takehiko; Nagy, András

doi:10.1016/s0014-5793(01)02663-1

Cited by 366 publications

(361 citation statements)

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“…The genes encoding granule proteases, such as Mcpt4,5,6,7, and cathepsin G (Ctsg), and enzymes involved in heparin biosynthesis, such as Ext1, Ndst2, Hs2st1, and Hs3st1, were downregulated in Hdc −/− pMCs, in good agreement with impaired granule maturation observed in Hdc −/− pMCs. Because we could not detect any significant changes in mRNA expression of several granule proteases with semiquantitative RT-PCR analysis previously [9], quantitative RT-PCR analysis was performed in this study. Expression of granule protease genes, such as Mcpt4,5,6,7, and Ctsg, was found to be decreased (<30% of the WT) in Hdc −/− pMCs (Fig.…”

Section: Characterization Of the Pmcs In Hdc −/− Micementioning

confidence: 96%

Histamine synthesis is required for granule maturation in murine mast cells

et al. 2013

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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 H 4 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. [6,7]. In a mouse mastocytoma P-815 cells, caspase-9-mediated cleavage results in enzymatic activation of HDC [8]. KeywordsWe have explored novel functions of histamine using a mouse strain lacking the Hdc gene. In the first report of Hdc −/− mice, we noticed that peritoneal mast cells (pMCs) and skin mast cells exhibited an aberrant morphology with severely decreased granule contents [9]. Although several studies indicated that mast cells express specific histamine receptors, it remains unknown how histamine affects the nature of mast cells. On the other hand, positive modulators for growth and differentiation of mast cells, such as IL-3 and c-kit ligand (Kitl), were found to induce a transient increase in histamine synthesis [10,11], raising a possibility that histamine is involved in the process of mast cell maturation. We hypothesized that newly synthesized histamine may play a critical role in granule maturation of mast cells in an autocrine fashion. We, here, took two different approaches to investigate the mechanism underlying the histamine-mediated promotion of granule maturation of mast cells; an in vitro approach using a mast cell fibroblast coculture model and an in vivo one using the mast cell reconstitution system with mast cell deficient Kit W /Kit W-v mice. This study proposes a novel function of histamine in mast cell biology. Results Characterization of the pMCs in Hdc −/− miceWe previously reported that the cutaneous and pMCs of Hdc −/− mice demonstrate aberrant granules with severely decreased contents [9]. pMCs in Hdc −/− mice were poorly-stained with Safranin-O and acidic Toluidine blue, compared with those in WT mice (Fi...

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Section: Characterization Of the Pmcs In Hdc −/− Micementioning

confidence: 96%

Histamine synthesis is required for granule maturation in murine mast cells

et al. 2013

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“…Mice lacking histidine decarboxylase (HDC À / À ) and the corresponding wild typestrain (HDC þ / þ ) on a 129/Sv background (18-22 g) were a kind gift from Dr. Ohtsu, Japan (Ohtsu et al, 2001). These animals were housed, four to six to a cage, in standard transparent laboratory cages.…”

Section: Animalsmentioning

confidence: 99%

In the brain of mice, 3-iodothyronamine (T1AM) is converted into 3-iodothyroacetic acid (TA1) and it is included within the signaling network connecting thyroid hormone metabolites with histamine

Laurino

Siena

Chiellini

et al. 2015

European Journal of Pharmacology

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“…during the light phase [16]. These mice were generated according to procedures previously described [51] and their genotypes confirmed using PCR. The doses used for amphetamine, modafinil and ciproxifan were 1, 32 and 1 mg/kg respectively as these approximated equal potency in terms of wake induction.…”

Section: Characterization Of the Wake-promoting Agents With Referencementioning

confidence: 99%