Regulation of plasma histamine levels by the mast cell clock and its modulation by stress

Yuki Nakamura, Kayoko Ishimaru, Shigenobu Shibata, Atsuhito Nakao

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell-deficient mice and their circadian variations were lost in mast cell-deficient mice reconstituted with bone marrow-derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80-induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell-mediated allergic reactions.

    Original languageEnglish
    Article number39934
    JournalScientific Reports
    Volume7
    DOIs
    Publication statusPublished - 2017 Jan 11

    Fingerprint

    Mast Cells
    Histamine
    Cations
    Circadian Clocks
    p-Methoxy-N-methylphenethylamine
    Hypersensitivity
    Bone Marrow
    Light
    Mutation
    Genes

    ASJC Scopus subject areas

    • General

    Cite this

    Regulation of plasma histamine levels by the mast cell clock and its modulation by stress. / Nakamura, Yuki; Ishimaru, Kayoko; Shibata, Shigenobu; Nakao, Atsuhito.

    In: Scientific Reports, Vol. 7, 39934, 11.01.2017.

    Research output: Contribution to journalArticle

    @article{493cebd77cc84389b4cbd7964aee4da2,
    title = "Regulation of plasma histamine levels by the mast cell clock and its modulation by stress",
    abstract = "At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell-deficient mice and their circadian variations were lost in mast cell-deficient mice reconstituted with bone marrow-derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80-induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell-mediated allergic reactions.",
    author = "Yuki Nakamura and Kayoko Ishimaru and Shigenobu Shibata and Atsuhito Nakao",
    year = "2017",
    month = "1",
    day = "11",
    doi = "10.1038/srep39934",
    language = "English",
    volume = "7",
    journal = "Scientific Reports",
    issn = "2045-2322",
    publisher = "Nature Publishing Group",

    }

    TY - JOUR

    T1 - Regulation of plasma histamine levels by the mast cell clock and its modulation by stress

    AU - Nakamura, Yuki

    AU - Ishimaru, Kayoko

    AU - Shibata, Shigenobu

    AU - Nakao, Atsuhito

    PY - 2017/1/11

    Y1 - 2017/1/11

    N2 - At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell-deficient mice and their circadian variations were lost in mast cell-deficient mice reconstituted with bone marrow-derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80-induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell-mediated allergic reactions.

    AB - At steady state, plasma histamine levels exhibit circadian variations with nocturnal peaks, which is implicated in the nighttime exacerbation of allergic symptoms. However, the regulatory mechanisms are largely unexplored. This study determined how steady-state plasma histamine levels are regulated and affected by environmental factors. We found that plasma histamine levels decreased in mast cell-deficient mice and their circadian variations were lost in mast cell-deficient mice reconstituted with bone marrow-derived mast cells (BMMCs) harboring a mutation in the circadian gene Clock. Clock temporally regulates expression of organic cation transporter 3 (OCT3), which is involved in histamine transport, in mast cells; OCT inhibition abolished circadian variations in plasma histamine levels. Mice housed under aberrant light/dark conditions or suffering from restraint stress exhibited de-synchronization of the mast cell clockwork, concomitant with the loss of circadian variations in OCT3 expression and plasma histamine levels. The degree of compound 48/80-induced plasma extravasation in mice was correlated with plasma histamine levels. Collectively, the mast cell clock mediates circadian regulation of plasma histamine levels at steady state, in part by controlling OCT3 expression, which can be modulated by stress. Additionally, we propose that plasma histamine levels potentiate mast cell-mediated allergic reactions.

    UR - http://www.scopus.com/inward/record.url?scp=85009195013&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85009195013&partnerID=8YFLogxK

    U2 - 10.1038/srep39934

    DO - 10.1038/srep39934

    M3 - Article

    C2 - 28074918

    AN - SCOPUS:85009195013

    VL - 7

    JO - Scientific Reports

    JF - Scientific Reports

    SN - 2045-2322

    M1 - 39934

    ER -