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Imaging protective mast cells in living mice during severe contact hypersensitivity.

ABSTRACT: Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in living mice, and permits the identification of such MCs as a potential source of cytokines in different disease models. We show using this method that dermal MCs release their granules progressively into the surrounding microenvironment, but also represent an initial source of the antiinflammatory cytokine IL-10, during the early phase of severe CHS reactions. Finally, using 3 different types of MC-deficient mice, as well as mice in which IL-10 is ablated specifically in MCs, we show that IL-10 production by MCs can significantly limit the inflammation and tissue pathology observed in severe CHS reactions.

SUBMITTER: Reber LL

PROVIDER: S-EPMC5414565 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Imaging protective mast cells in living mice during severe contact hypersensitivity.

Reber Laurent L LL Sibilano Riccardo R Starkl Philipp P Roers Axel A Grimbaldeston Michele A MA Tsai Mindy M Gaudenzio Nicolas N Galli Stephen J SJ

JCI insight 20170504 9

Contact hypersensitivity (CHS) is a common skin disease induced by epicutaneous sensitization to haptens. Conflicting results have been obtained regarding pathogenic versus protective roles of mast cells (MCs) in CHS, and this has been attributed in part to the limitations of certain models for studying MC functions in vivo. Here we describe a fluorescent imaging approach that enables in vivo selective labeling and tracking of MC secretory granules by real-time intravital 2-photon microscopy in ...[more]

PMID: 28469089

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Project description:Cancer pain induced by pancreatic carcinoma is one of the most common symptoms and is difficult to endure, especially in the advanced stage. Evidence suggests that mast cells are recruited and degranulate in enteric disease-related visceral hypersensitivity. However, whether mast cells promote the visceral pain induced by pancreatic carcinoma remains unclear. Here, using toluidine blue staining and western blotting, we observed that mast cells were dramatically recruited to tissues surrounding pancreatic carcinoma, but not inside the carcinoma in patients with severe visceral pain. The levels of mast cell degranulation products, including tryptase, histamine, and nerve growth factor, were significantly increased in pericarcinoma tissues relative to their levels in normal controls, as evidenced by enzyme-linked immunosorbent assay. We determined that systemic administration of mast cell secretagogue compound 48/80 exacerbated pancreatic carcinoma-induced visceral hypersensitivity in a male BALB/c nude mouse model as assessed by measuring the hunching behavior scores and mechanical withdrawal response frequency evoked by von Frey stimulation. In contrast, the mast cell stabilizer ketotifen dose-dependently alleviated pancreatic cancer pain. In addition, we observed incomplete development of abdominal mechanical hyperalgesia and hunching behavior in mast cell-deficient mice with pancreatic carcinoma. However, ketotifen did not further attenuate visceral hypersensitivity in mast cell-deficient mice with carcinoma. Finally, we confirmed that intraplantar injection of pericarcinoma supernatants from BALB/c nude mice but not mast cell-deficient mice caused acute somatic nociception. In conclusion, our findings suggest that mast cells contribute to pancreatic carcinoma-induced visceral hypersensitivity through enrichment and degranulation in pericarcinoma tissues. The inhibition of mast cell degranulation may be a potential strategy for the therapeutic treatment of pancreatic carcinoma-induced chronic visceral pain.

Dataset Information

Imaging protective mast cells in living mice during severe contact hypersensitivity.

Publications

Imaging protective mast cells in living mice during severe contact hypersensitivity.

Similar Datasets

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