Uptake of histamine by mouse peritoneal macrophages and a macrophage cell  line, RAW264.7

Tanaka, Satoshi; Deai, Katsuya; Inagaki, Mariko; Ichikawa, Atsushi

doi:10.1152/ajpcell.00470.2002

Cited by 20 publications

(13 citation statements)

References 22 publications

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“…3C). These results are reminiscent of the previous studies that showed influx of extracellular histamine through organic cation transporter(s) (OCT) with low affinity and high capacity for histamine, such as OCT-3 [13,14]. An increase in the cytosolic histamine might result in accumulation of histamine in the granules.…”

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

confidence: 78%

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: Impaired Granule Maturation Of Hdc −/− Ctmc Like Cultured Masupporting

confidence: 78%

Histamine synthesis is required for granule maturation in murine mast cells

et al. 2013

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“…This system may contribute not only to feedback inhibition of histamine synthesis but also to suppression of Th2 cytokine production by immature basophils. Histamine transport across the plasma membrane was also reported in the other studies, indicating the involvement of OCT2 and an unknown system other than the OCT / OCTN family in addition to OCT3 (46,47).…”

Section: Mast Cells and Basophilssupporting

confidence: 74%

Recent Advances in Molecular Pharmacology of the Histamine Systems: Immune Regulatory Roles of Histamine Produced by Leukocytes

Tanaka

Ichikawa

2006

J Pharmacol Sci

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Abstract. Accumulating evidence has highlighted the importance of histamine in immune responses. The H 1 receptor is involved not only in allergic inflammatory reactions but also in augmentation of helper T cell (Th)1 responses, whereas H 2 receptor suppresses Th responses and participates in immune tolerance through interleukin-10 and transforming growth factor-β. Identification of the H 4 receptor, which binds to histamine with high affinity and of which expression is limited to the hematopoietic system, has enhanced the importance of histamine in immune responses. However, since a majority of previous studies has evaluated the effects of exogenous histamine, it remains largely unknown how endogenously produced histamine is involved in regulation of such kinds of immune responses. Insight into precise roles of histamine in the immune system can not be obtained without correct understanding of both the predominance of a certain type of histamine receptor and the regulation of histamine synthesis. Here we review a part of the recent progress in histamine research in the field of immunology with attention to the source of involved histamine.

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“…However, histamine content in the tissues of HDC −/− mice was controllable through dietary supplementation of histamine. 41,42) We found that dietary histamine accumulated in the spleen of HDC −/− mice and that macrophages were responsible for this uptake. 42) …”

Section: Regulation Of Histamine Synthesismentioning

confidence: 79%

Molecular biology of histidine decarboxylase and prostaglandin receptors

Ichikawa

Sugimoto

Tanaka

2010

Proc. Jpn. Acad., Ser. B

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Histamine and prostaglandins (PGs) play a variety of physiological roles as autacoids, which function in the vicinity of their sources and maintain local homeostasis in the body. They stimulate target cells by acting on their specific receptors, which are coupled to trimeric G proteins. For the precise understanding of the physiological roles of histamine and PGs, it is necessary to clarify the molecular mechanisms involved in their synthesis as well as their receptor-mediated responses. We cloned the cDNAs for mouse l-histidine decarboxylase (HDC) and 6 mouse prostanoid receptors (4 PGE2 receptors, PGF receptor, and PGI receptor). We then characterized the expression patterns and functions of these genes. Furthermore, we established gene-targeted mouse strains for HDC and PG receptors to explore the novel pathophysiological roles of histamine and PGs. We have here summarized our research, which should contribute to progress in the molecular biology of HDC and PG receptors.

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Uptake of histamine by mouse peritoneal macrophages and a macrophage cell line, RAW264.7

Cited by 20 publications

References 22 publications

Histamine synthesis is required for granule maturation in murine mast cells

Histamine synthesis is required for granule maturation in murine mast cells

Recent Advances in Molecular Pharmacology of the Histamine Systems: Immune Regulatory Roles of Histamine Produced by Leukocytes

Molecular biology of histidine decarboxylase and prostaglandin receptors

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