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Histamine‐mediated regulatory loop in mesenteric perilymphatic mast cells
Author(s) -
Gashev Anatoliy A.,
Gasheva Olga Yu.,
Zawieja David C.,
Meininger Cynthia J.,
Pal Sarit
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02764
Subject(s) - histamine , degranulation , mast cell , inflammation , autocrine signalling , immunology , lymphatic system , immune system , histamine receptor , microbiology and biotechnology , biology , chemistry , receptor , medicine , pharmacology , antagonist
Lymphatic vessels play a critical role in mounting a proper immune response by trafficking peripheral immune cells to draining lymph nodes. Mast cells (MCs) are well known for their roles in type I hypersensitivity reactions but little is known about their secretory regulation in the lymphatic niche. MCs, as innate sensor and effector cells, reside close to mesenteric lymphatic vessels (MLVs) and their activation and ability to release histamine influences the lymphatic microenvironment in a histamine‐NF‐kB‐dependent manner. Using an established experimental protocol involving surgical isolation of rat mesenteric tissue segments, including MLVs and surrounding perilymphatic tissues, we tested the hypothesis that perilymphatic mesenteric MCs possess histamine receptors (HRs) that bind and respond to histamine released from these same MCs. Under various experimental conditions, including inflammatory stimulation by LPS, we measured histamine in mesenteric perilymphatic tissues, evaluated expression of histidine decarboxylase in MCs along with the degree of MC degranulation, assessed the functional status of HRs in MCs, and evaluated the ability of histamine itself to induce MC activation. Finally, we evaluated the importance of MCs and HRs 1 and 2 for MLV‐directed trafficking of CD11b/c‐positive cells during acute tissue inflammation. Our data indicate the existence of a functionally potent MC‐histamine autocrine regulatory loop, the elements of which are crucially important for acute inflammation‐induced trafficking of the CD11b/c‐positive cells towards MLVs. Our previously published data suggest that MLVs‐released histamine can also trigger the MC‐histamine loop during development of inflammation. Therefore, this MC‐histamine loop serves as a first‐line cellular servo control system, playing a key role in the innate and adaptive immune response as well as NF‐κB‐mediated maintenance of body homeostasis. Support or Funding Information NIH/NIA R56 AG061097‐01; NIH/NIDDK R01 DK110035; NIH/NHLBI 1U01HL123420; funds from TAMU HSC COM and Dept. of Medical Physiology.