Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue‐type mast cells

Takano, Hirotsugu; Nakazawa, Shunsuke; Okuno, Yasushi; Shirata, Naritoshi; Tsuchiya, Shogo; Kainoh, Takayuki; Takamatsu, Seigoh; Furuta, Kazuyuki; Taketomi, Yoshitaka; Naito, Yuko; Takematsu, Hiromu; Kozutsumi, Yasunori; Tsujimoto, Gozoh; Murakami, Makoto; Kudo, Ichiro; Ichikawa, Atsushi; Nakayama, Kazuhisa; Sugimoto, Yukihiko; Tanaka, Satoshi

doi:10.1016/j.febslet.2008.03.033

Cited by 42 publications

(68 citation statements)

References 32 publications

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“…This modification is catalyzed by transglutaminase-2 (TGM2). Since histamine synthesis was transiently induced and Tgm2 is upregulated during the coculture period in our system [12], it is possible that histaminylation of the cytosolic proteins by TGM-2, which can target and activate Gα o1 and Cdc42, is involved in granule maturation of mast cells.…”

Section: Discussionmentioning

confidence: 99%

“…We have recently established a culture model that can reproduce at least in part the process of maturation of connective tissue-type mast cells (CTMCs); in this model, BMMCs are cocultured with mitomycin C-treated Swiss 3T3 fibroblasts in the presence of Kitl [12]. Induction of HDC during the coculture period raised a possibility that transiently induced histamine synthesis results in granule maturation of mast cells.…”

Section: Impaired Granule Maturation Of Hdc −/− Ctmc Like Cultured Mamentioning

confidence: 99%

“…Enzyme activity of β-hexosaminidase and three kinds of granule proteases were measured as described previously [12]. Total β-hexosaminidase activity in peritoneal cells and BMMCs was not significantly different between WT and Hdc −/− mice.…”

Section: Degranulation and Granule Protease Assaymentioning

confidence: 99%

“…A CTMC culture model was originally established through coculture of BMMCs with Swiss 3T3 fibroblasts [33,34]. We modified this culture method and obtained CTMC-like cultured mast cells using mitomycin C-treated Swiss 3T3 fibroblasts in the presence of Kitl (30 ng/mL) as previously described [12].…”

Section: Preparation Of Bmmcs and Ctmc-like Mcsmentioning

confidence: 99%

“…BMMCs were prepared as previously described [12]. Briefly, BM cells were cultured in the presence of 10 ng/mL IL-3 for 30-35 days to obtain mature BMMCs.…”

Section: Preparation Of Bmmcs and Ctmc-like Mcsmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Impaired Granule Maturation Of Hdc −/− Ctmc Like Cultured Mamentioning

confidence: 99%

Section: Degranulation and Granule Protease Assaymentioning

confidence: 99%

Section: Preparation Of Bmmcs and Ctmc-like Mcsmentioning

confidence: 99%

“…BMMCs were prepared as previously described [12]. Briefly, BM cells were cultured in the presence of 10 ng/mL IL-3 for 30-35 days to obtain mature BMMCs.…”

Section: Preparation Of Bmmcs and Ctmc-like Mcsmentioning

confidence: 99%

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Histamine synthesis is required for granule maturation in murine mast cells

et al. 2013

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1‐Fluoro‐2,4‐dinitrobenzene and its derivatives act as secretagogues on rodent mast cells

et al. 2016

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Accumulating evidence suggests that activated mast cells are involved in contact hypersensitivity, although the precise mechanisms of their activation are still not completely understood. We investigated the potential of common experimental allergens to induce mast cell activation using murine bone marrow-derived cultured mast cells and rat peritoneal mast cells. Among these allergens, 1-chloro-2,4-dinitrobenzene and 1-fluoro-2,4-dinirobenzene (DNFB) were found to induce degranulation of rat peritoneal mast cells. DNFB-induced degranulation is accompanied by cytosolic Ca 2+ mobilization and is significantly inhibited by pertussis toxin, U73122 (a phospholipase C inhibitor), and BAPTA (a Ca 2+ chelator), raising the possibility that DNFB acts on the G protein-coupled receptors and activates G i , which induces activation of phospholipase C, as well as known mast cell secretagogues, such as compound 48/80. DNFB could induce mast cell degranulation in the absence of serum proteins and IgE. Structure-activity relationship analyses revealed an inverse correlation between the degree of degranulation and the electron density of the C1 carbon of the DNFB derivatives. These findings raise a possibility that DNFB functions as a potent contact allergen through induction of cutaneous mast cell degranulation.Keywords: Contact hypersensitivity r 1-Fluoro-2,4-dinitrobenzene r Histamine r Inflammation r Mast cells Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Prof. Satoshi Tanaka e-mail: tanaka-s@okayama-u.ac.jp IntroductionA series of recent studies have enriched our understanding about the pathology of contact hypersensitivity [1]. Contact hypersensitivity was initially recognized as an allergic responses induced C 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2017. 47: 60-67 Innate immunity 61 mainly by activated T cells but now is regarded as the complex process involving many kinds of immune cells in addition to T cells. Chemical compounds, such as 1-fluoro-2,4-dinitrobenzene (DNFB), oxazolone, and picryl chloride, have been used for induction of contact hypersensitivity [2]. These models have revealed that self-proteins conjugated with these compounds induced Tcell-mediated immune responses, which required dendritic cell migration. Although it has long been controversial whether mast cells are involved in contact hypersensitivity, a series of the transfer experiments has indicated that IgE and mast cells could initiate immune responses in several models [3,4]. Recent studies have expanded the pathological roles of IgE and cutaneous mast cells in murine contact hypersensitivity models [5,6]. Bryce et al. demonstrated that successful contact hypersensitivity with oxazolone should require mast cells equipped with IgE [7]. Cutaneous mast cells were found to promote dendritic cell migration into the draining lymph node, which is regarded as the primary step of contact hypersensitivity, through the release...

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Mast cells in type 2 skin inflammation: Maintenance and function

et al. 2023

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Mast cells (MCs) are immune cells residing in tissues and playing indispensable roles in maintaining homeostasis and inflammatory states. Skin lesions associated with atopic dermatitis (AD) and type 2 skin inflammation display an increment in MCs, which have both pro‐ and anti‐inflammatory effects. The direct and indirect activations of skin MCs by environmental factors such as Staphylococcus aureus can instigate type 2 skin inflammation in AD with poorly understood mechanisms. Furthermore, both IgE‐dependent and ‐independent degranulation of MCs contribute to pruritus in AD. Conversely, MCs suppress type 2 skin inflammation by promoting Treg expansion through IL‐2 secretion in the spleen. Moreover, skin MCs can upregulate gene expression involved in skin barrier function, thus mitigating AD‐like inflammation. These functional variances of MCs in AD could stem from differences in experimental systems, their localization, and origins. In this review, we will focus on how MCs are maintained in the skin under homeostatic and inflammatory conditions, and how they are involved in the pathogenesis of type 2 skin inflammation.

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Establishment of the culture model system that reflects the process of terminal differentiation of connective tissue‐type mast cells

Cited by 42 publications

References 32 publications

Histamine synthesis is required for granule maturation in murine mast cells

Histamine synthesis is required for granule maturation in murine mast cells

1‐Fluoro‐2,4‐dinitrobenzene and its derivatives act as secretagogues on rodent mast cells

Mast cells in type 2 skin inflammation: Maintenance and function

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