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Histamine Synthesis and Lessons Learned from Histidine Decarboxylase Deficient Mice

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Histamine in Inflammation

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 709))

Abstract

This chapter summarizes the information about the transcriptional regulation of histidine decarboxylase (HDC), which is the catabolic enzyme of histamine synthesis, and the activity of histamine in vivo as clarified using HDC gene deficient mice (HDC-KO). The research of the regulatory mechanism of histamine synthesis has been focused on transcriptional and posttranslational aspects. The generation of HDC-KO mice clarified several new pathophysiological functions of histamine. It is now recognized that the activity of histamine is not limited to allergic, peptic and neurological functions as in the old paradigm, but extends to other fields such as cardiology, immunology and infectious diseases. Therefore, this chapter will focus on these newly revealed functions of histamine. For example, histamine was known to be involved in the effector phase of allergic responses, but a role has now been shown in the sensitization phases and in innate immunity. In the allergic bronchial asthma model using HDC-KO mice it was found that histamine positively controls eosinophilia, but not bronchial hypersensitivity. The effect on eosinophils was afterwards shown to be mediated through the activity of the histamine H4 receptor. The recent advances in the understanding of histamine synthesis and the activity of HDC have dramatically expanded our understanding of the scope of histamine function.

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References

  1. Dale HH, Laidlaw PP. The physiological action of beta-iminazolylethylamine. J Physiol 1910; 41(5):318–344.

    PubMed  CAS  Google Scholar 

  2. Dale HH, Laidlaw PP. Further observations on the action of beta-iminazolylethylamine. J Physiol 1911; 43(2):182–195.

    PubMed  CAS  Google Scholar 

  3. Moya-Garcia AA, Medina MA, Sanchez-Jimenez F. Mammalian histidine decarboxylase: from structure to function. Bioessays 2005; 27(1):57–63.

    Article  PubMed  CAS  Google Scholar 

  4. Suzuki-Ishigaki S, Numayama-Tsuruta K, Kuramasu A et al. The mouse l-histidine decarboxylase gene: structure and transcriptional regulation by CpG methylation in the promoter region. Nucleic Acids Res 2000; 28(14):2627–2633.

    Article  PubMed  CAS  Google Scholar 

  5. Kuramasu A, Saito H, Suzuki S et al. Mast cell-/basophil-specific transcriptional regulation of human l-histidine decarboxylase gene by CpG methylation in the promoter region. J Biol Chem 1998; 273(47):31607–31614.

    Article  PubMed  CAS  Google Scholar 

  6. Fleming JV, Fajardo I, Langlois MR et al. The C-terminus of rat l-histidine decarboxylase specifically inhibits enzymic activity and disrupts pyridoxal phosphate-dependent interactions with l-histidine substrate analogues. Biochem J 2004; 381(Pt 3):769–778.

    Article  PubMed  CAS  Google Scholar 

  7. Olmo MT, Urdiales JL, Pegg AE et al. In vitro study of proteolytic degradation of rat histidine decarboxylase. Eur J Biochem 2000; 267(5):1527–1531.

    Article  PubMed  CAS  Google Scholar 

  8. Furuta K, Nakayama K, Sugimoto Y et al. Activation of histidine decarboxylase through posttranslational cleavage by caspase-9 in a mouse mastocytoma P-815. J Biol Chem 2007; 282(18):13438–13446.

    Article  PubMed  CAS  Google Scholar 

  9. Zhang Z, Hocker M, Koh TJ et al. The human histidine decarboxylase promoter is regulated by gastrin and phorbol 12-myristate 13-acetate through a downstream cis-acting element. J Biol Chem 1996; 271(24):14188–14197.

    Article  PubMed  CAS  Google Scholar 

  10. Hocker M, Henihan RJ, Rosewicz S et al. Gastrin and phorbol 12-myristate 13-acetate regulate the human histidine decarboxylase promoter through Raf-dependent activation of extracellular signal-regulated kinase-related signaling pathways in gastric cancer cells. J Biol Chem 1997; 272(43):27015–27024.

    Article  PubMed  CAS  Google Scholar 

  11. Hocker M, Zhang Z, Fenstermacher DA et al. Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway. Am J Physiol 1996; 270(4 Pt 1):G619–G633.

    PubMed  CAS  Google Scholar 

  12. Ohgoh M, Yamamoto J, Kawata M et al. Enhanced expression of the mouse l-histidine decarboxylase gene with a combination of dexamethasone and 12-O-tetradecanoylphorbol-13-acetate. Biochem Biophys Res Commun 1993; 196(3):1113–1119.

    Article  PubMed  CAS  Google Scholar 

  13. Hocker M, Rosenberg I, Xavier R et al. Oxidative stress activates the human histidine decarboxylase promoter in AGS gastric cancer cells. J Biol Chem 1998; 273(36):23046–23054.

    Article  PubMed  CAS  Google Scholar 

  14. Pacilio M, Debili N, Arnould A et al. Thrombopoietin induces histidine decarboxylase gene expression in c-mpl transfected UT7 cells. Biochem Biophys Res Commun 2001; 285(5):1095–1101.

    Article  PubMed  CAS  Google Scholar 

  15. Fukui H, Fujimoto K, Mizuguchi H et al. Molecular cloning of the human histamine H1 receptor gene. Biochem Biophys Res Commun 1994; 201(2):894–901.

    Article  PubMed  CAS  Google Scholar 

  16. Gantz I, Munzert G, Tashiro T et al. Molecular cloning of the human histamine H2 receptor. Biochem Biophys Res Commun 1991; 178(3):1386–1392.

    Article  PubMed  CAS  Google Scholar 

  17. Lovenberg TW, Roland BL, Wilson SJ et al. Cloning and functional expression of the human histamine H3 receptor. Mol Pharmacol 1999; 55(6):1101–1107.

    PubMed  CAS  Google Scholar 

  18. Oda T, Morikawa N, Saito Y et al. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J Biol Chem 2000; 275(47):36781–36786.

    Article  PubMed  CAS  Google Scholar 

  19. Huang JF, Thurmond RL. The new biology of histamine receptors. Curr Allergy Asthma Rep 2008; 8(1):21–27.

    Article  PubMed  CAS  Google Scholar 

  20. Taguchi Y, Watanabe T, Kubota H et al. Purification of histidine decarboxylase from the liver of fetal rats and its immunochemical and immunohistochemical characterization. J Biol Chem 1984; 259(8):5214–5221.

    PubMed  CAS  Google Scholar 

  21. Martin SA, Bishop JO. Purification and characterization of histidine decarboxylase from mouse kidney. Biochem J 1986; 234(2):349–354.

    PubMed  CAS  Google Scholar 

  22. Joseph DR, Sullivan PM, Wang YM et al. Characterization and expression of the complementary DNA encoding rat histidine decarboxylase. Proc Natl Acad Sci USA 1990; 87(2):733–737.

    Article  PubMed  CAS  Google Scholar 

  23. Yatsunami K, Tsuchikawa M, Kamada M et al. Comparative studies of human recombinant 74-and 54-kDa l-histidine decarboxylases. J Biol Chem 1995; 270(51):30813–30817.

    Article  PubMed  CAS  Google Scholar 

  24. Fleming JV, Wang TC. The production of 53-55-kDa isoforms is not required for rat l-histidine decarboxylase activity. J Biol Chem 2003; 278(1):686–694.

    Article  PubMed  CAS  Google Scholar 

  25. Yatsunami K, Ohtsu H, Tsuchikawa M et al. Structure of the l-histidine decarboxylase gene. J Biol Chem 1994; 269(2):1554–1559.

    PubMed  CAS  Google Scholar 

  26. Ai W, Liu Y, Langlois M et al. Kruppel-like factor 4 (KLF4) represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elements. J Biol Chem 2004; 279(10):8684–8693.

    Article  PubMed  CAS  Google Scholar 

  27. Ohtsu H, Kuramasu A, Suzuki S et al. Histidine decarboxylase expression in mouse mast cell line P815 is induced by mouse peritoneal cavity incubation. J Biol Chem 1996; 271(45):28439–28444.

    Article  PubMed  CAS  Google Scholar 

  28. Ai W, Zheng H, Yang X et al. Tip60 functions as a potential corepressor of KLF4 in regulation of HDC promoter activity. Nucleic Acids Res. 2007; 35(18):6137–6149.

    Article  PubMed  CAS  Google Scholar 

  29. Norlen P, Ericsson P, Kitano M et al. The vagus regulates histamine mobilization from rat stomach ECL cells by controlling their sensitivity to gastrin. J Physiol 2005; 564(Pt 3):895–905.

    Article  PubMed  CAS  Google Scholar 

  30. Prinz C, Zanner R, Gratzl M. Physiology of gastric enterochromaffin-like cells. Annu Rev Physiol 2003; 65:371–382.

    Article  PubMed  CAS  Google Scholar 

  31. Tanaka S, Hamada K, Yamada N et al. Gastric acid secretion in l-histidine decarboxylase-deficient mice. Gastroenterology 2002; 122(1):145–155.

    Article  PubMed  CAS  Google Scholar 

  32. Jeong HJ, Moon PD, Kim SJ et al. Activation of hypoxia-inducible factor-1 regulates human histidine decarboxylase expression. Cell Mol Life Sci 2009; 66(7):1309–1319.

    Article  PubMed  CAS  Google Scholar 

  33. Ohtsu H, Tanaka S, Terui T et al. Mice lacking histidine decarboxylase exhibit abnormal mast cells. FEBS Lett 2001; 502(1–2):53–56.

    Article  PubMed  CAS  Google Scholar 

  34. Hirasawa N, Ohtsu H, Watanabe T et al. Enhancement of neutrophil infiltration in histidine decarboxylase-deficient mice. Immunology 2002; 107(2):217–221.

    Article  PubMed  CAS  Google Scholar 

  35. Koarai A, Ichinose M, Ishigaki-Suzuki S et al. Disruption of l-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness. Am J Respir Crit Care Med 2003; 167(5):758–763.

    Article  PubMed  Google Scholar 

  36. Makabe-Kobayashi Y, Hori Y, Adachi T et al. The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis. J Allergy Clin Immunol 2002; 110(2):298–303.

    Article  PubMed  CAS  Google Scholar 

  37. Parmentier R, Ohtsu H, Djebbara-Hannas Z et al. Anatomical, physiological and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. J Neurosci 2002; 22(17):7695–7711.

    PubMed  CAS  Google Scholar 

  38. Dere E, De Souza-Silva MA, Spieler RE et al. Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5-HT turnover in histidine decarboxylase-KO mice. Eur J Neurosci 2004; 20(4):1051–1058.

    Article  PubMed  CAS  Google Scholar 

  39. Jutel M, Watanabe T, Klunker S et al. Histamine regulates T-cell and antibody responses by differential expression of H1 and H2 receptors. Nature 2001; 413(6854):420–425.

    Article  PubMed  CAS  Google Scholar 

  40. Pedotti R, De Voss JJ, Steinman L et al. Involvement of both ‘allergic’ and ‘autoimmune’ mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol 2003; 24(9):479–484.

    Article  PubMed  CAS  Google Scholar 

  41. Gutzmer R, Diestel C, Mommert S et al. Histamine H4 receptor stimulation suppresses IL-12p70 production and mediates chemotaxis in human monocyte-derived dendritic cells. J Immunol 2005; 174(9):5224–5232.

    PubMed  CAS  Google Scholar 

  42. Damaj BB, Becerra CB, Esber HJ et al. Functional expression of H4 histamine receptor in human natural killer cells, monocytes and dendritic cells. J Immunol 2007; 179(11):7907–7915.

    PubMed  CAS  Google Scholar 

  43. Leite-de-Moraes MC, Diem S, Michel ML et al. Cutting edge: Histamine receptor H4 activation positively regulates in vivo IL-4 and IFN-gamma production by invariant NKT cells. J Immunol 2009; 182(3):1233–1236.

    PubMed  CAS  Google Scholar 

  44. Numata Y, Terui T, Okuyama R et al. The accelerating effect of histamine on the cutaneous wound-healing process through the action of basic fibroblast growth factor. J Invest Dermatol 2006; 126(6):1403–1409.

    Article  PubMed  CAS  Google Scholar 

  45. Willadsen P, Wood GM, Riding GA. The relation between skin histamine concentration, histamine sensitivity and the resistance of cattle to the tick, Boophilus microplus. Z Parasitenkd 1979; 59(1):87–93.

    Article  PubMed  CAS  Google Scholar 

  46. Hirokawa K, Aoki N. Up-regulation of thrombomodulin by activation of histamine H1-receptors in human umbilical-vein endothelial cells in vitro. Biochem J 1991; 276(Pt 3):739–743.

    PubMed  CAS  Google Scholar 

  47. Beghdadi W, Porcherie A, Schneider BS et al. Inhibition of histamine-mediated signaling confers significant protection against severe malaria in mouse models of disease. J Exp Med 2008; 205(2):395–408.

    Article  PubMed  CAS  Google Scholar 

  48. Andou A, Hisamatsu T, Okamoto S et al. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology 2009; 136(2):564–574 e562.

    Article  PubMed  CAS  Google Scholar 

  49. White MV. The role of histamine in allergic diseases. J Allergy Clin Immunol 1990; 86(4 Pt 2):599–605.

    Article  PubMed  CAS  Google Scholar 

  50. Gutzmer R, Langer K, Lisewski M et al. Expression and function of histamine receptors 1 and 2 on human monocyte-derived dendritic cells. J Allergy Clin Immunol 2002; 109(3):524–531.

    Article  PubMed  CAS  Google Scholar 

  51. Caron G, Delneste Y, Roelandts E et al. Histamine polarizes human dendritic cells into Th2 cell-promoting effector dendritic cells. J Immunol 2001; 167(7):3682–3686.

    PubMed  CAS  Google Scholar 

  52. Mazzoni A, Young HA, Spitzer JH et al. Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T-cell polarization. J Clin Invest 2001; 108(12): 1865–1873.

    PubMed  CAS  Google Scholar 

  53. Elenkov IJ, Webster E, Papanicolaou DA et al. Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. J Immunol 1998; 161(5):2586–2593.

    PubMed  CAS  Google Scholar 

  54. van der Pouw Kraan TC, Snijders A, Boeije LC et al. Histamine inhibits the production of interleukin-12 through interaction with H2 receptors. J Clin Invest 1998; 102(10):1866–1873.

    Article  PubMed  Google Scholar 

  55. Dunford PJ, O’Donnell N, Riley JP et al. The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T-cells. J Immunol 2006; 176(11):7062–7070.

    PubMed  CAS  Google Scholar 

  56. O’Reilly M, Alpert R, Jenkinson S et al. Identification of a histamine H4 receptor on human eosinophils—role in eosinophil chemotaxis. J Recept Signal Transduct Res 2002; 22(1–4):431–448.

    PubMed  Google Scholar 

  57. Siraganian RP. Biochemical events in basophil/mast cell activation and medicator release. In: Adkinson NFJea, ed. Middleton’s Allergy. Philadelphia: Mosby; 2003:243–276.

    Google Scholar 

  58. Ishizaka T, Ishizaka K. Activation of mast cells for mediator release through IgE receptors. Prog Allergy 1984; 34:188–235.

    PubMed  CAS  Google Scholar 

  59. Ott VL, Cambier JC. Activating and inhibitory signaling in mast cells: new opportunities for therapeutic intervention? J Allergy Clin Immunol 2000; 106(3):429–440.

    Article  PubMed  CAS  Google Scholar 

  60. Kinet JP. The high-affinity receptor for IgE. Curr Opin Immunol 1989; 2(4):499–505.

    Article  PubMed  CAS  Google Scholar 

  61. Kaneko M, Schimming A, Gleich GJ et al. Ligation of IgE receptors causes an anaphylactic response and neutrophil infiltration but does not induce eosinophilic inflammation in mice. J Allergy Clin Immunol 2000; 105(6 Pt 1):1202–1210.

    Article  PubMed  CAS  Google Scholar 

  62. Nagai H, Abe T, Yamaguchi I et al. Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice. J Allergy Clin Immunol 2000; 106(1 Pt 2):S91–S98.

    Article  PubMed  CAS  Google Scholar 

  63. Higuchi S, Tanimoto A, Arima N et al. Effects of histamine and interleukin-4 synthesized in arterial intima on phagocytosis by monocytes/macrophages in relation to atherosclerosis. FEBS Lett 2001; 505(2):217–222.

    Article  PubMed  CAS  Google Scholar 

  64. Miyazawa N, Watanabe S, Matsuda A et al. Role of histamine H1 and H2 receptor antagonists in the prevention of intimal thickening. Eur J Pharmacol 1998; 362(1):53–59.

    Article  PubMed  CAS  Google Scholar 

  65. Sasaguri Y, Wang KY, Tanimoto A et al. Role of histamine produced by bone marrow-derived vascular cells in pathogenesis of atherosclerosis. Circ Res 2005; 96(9):974–981.

    Article  PubMed  CAS  Google Scholar 

  66. Corbel S, Schneider E, Lemoine FM et al. Murine hematopoietic progenitors are capable of both histamine synthesis and uptake. Blood 1995; 86(2):531–539.

    PubMed  CAS  Google Scholar 

  67. Ohtsu H, Kuramasu A, Tanaka S et al. Plasma extravasation induced by dietary supplemented histamine in histamine-free mice. Eur J Immunol 2002; 32(6): 1698–1708.

    Article  PubMed  CAS  Google Scholar 

  68. Schneider E, Machavoine F, Pleau JM et al. Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels. J Exp Med 2005; 202(3):387–393.

    Article  PubMed  CAS  Google Scholar 

  69. Travis ER, Wang YM, Michael DJ et al. Differential quantal release of histamine and 5-hydroxytryptamine from mast cells of vesicular monoamine transporter 2 knockout mice. Proc Natl Acad Sci USA 2000; 97(1):162–167.

    Article  PubMed  CAS  Google Scholar 

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Ohtsu, H. (2010). Histamine Synthesis and Lessons Learned from Histidine Decarboxylase Deficient Mice. In: Thurmond, R.L. (eds) Histamine in Inflammation. Advances in Experimental Medicine and Biology, vol 709. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-8056-4_3

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