Characterization and Function of Histamine Receptors in Human Bone Marrow Stromal Cells§

Authors

  • Krisztian Nemeth,

    Corresponding author
    1. National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
    • National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
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    • Telephone: 301-451-9880; Fax: 301-496-1339

  • Todd Wilson,

    1. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA
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  • Balazs Rada,

    1. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Rockville, Maryland, USA
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  • Alissa Parmelee,

    1. National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
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  • Balazs Mayer,

    1. National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
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  • Edit Buzas,

    1. Faculty of Medicine, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
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  • Andras Falus,

    1. Faculty of Medicine, Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary
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  • Sharon Key,

    1. National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
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  • Tamas Masszi,

    1. Szent Laszlo Hospital, Department of Hematology and Stem Cell Transplantation, Budapest, Hungary
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  • Sarolta Karpati,

    1. Department of Dermato-Venereology and Dermato-Oncology, Semmelweis University, Budapest, Hungary
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  • Eva Mezey

    Corresponding author
    1. National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
    • National Institutes of Dental and Craniofacial Research, Craniofacial and Skeletal Diseases Branch, NIH, Bethesda, Maryland, USA
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    • Telephone: 301-435-5635; Fax: 301-496-1339


  • Author contributions: K.N.: conception and design, collection, assembly, analysis and interpretation of data, and manuscript writing; T.W., E.B., A.F., T.M., and S.K.: provision of study material or patients; B.M.: performing and evaluating of RT-PCR and in vitro experiments and collection and/or assembly of data; B.R.: performing and evaluating superoxide assays; A.P.: collection and/or assembly of data; E.M.: conception and design, data analysis and interpretation, and illustrations and manuscript writing.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS November 1, 2011.

Abstract

There are several clinical trials worldwide using bone marrow stromal cells (BMSCs) as a cellular therapy to modulate immune responses in patients suffering from various inflammatory conditions. A deeper understanding of the molecular mechanisms involved in this modulatory effect could help us design better, more effective protocols to treat immune mediated diseases. In this study, we demonstrated that human BMSCs express H1, H2, and H4 histamine receptors and they respond to histamine stimulation with an increased interleukin 6 (IL-6) production both in vitro and in vivo. Using different receptor antagonists, we pinpointed the importance of the H1 histamine receptor, while Western blot analysis and application of various mitogen-activated protein kinase inhibitors highlighted the role of p38, extracellular signal-regulated kinase, and c-Jun N-terminal kinase kinases in the observed effect. When BMSCs were pretreated with either histamine or degranulated human mast cells, they exhibited an enhanced IL-6-dependent antiapoptotic effect on neutrophil granulocytes. Based on these observations, it is likely that introduction of BMSCs into a histamine-rich environment (such as any allergic setting) or pretreatment of these cells with synthetic histamine could have a significant modulatory effect on the therapeutic potential of BMSCs. STEM CELLS 2012; 30:222–231.

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