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Disparity in Fc?RI-induced degranulation of primary human lung and skin mast cells exposed to adenosine.

ABSTRACT: Inhaled and intravenously administered adenosine induces mast cell-mediated (histamine-dependent) bronchospasm in asthmatics without causing urticaria. A differential response to adenosine by human lung and skin mast cells is shown: low concentrations potentiate Fc?RI-induced degranulation of human lung mast cells but not that of skin mast cells. Human lung mast cells were found to express ? 3-fold more A3AR messenger RNA (mRNA) than skin mast cells, suggesting the involvement of the G(i)-linked A3AR. Indeed, the adenosine-induced potentiation was sensitive to inhibition by pertussis toxin and, furthermore, could be induced with an A3AR-specific agonist. This study reveals a previously unrecognized disparity in the response to adenosine by primary human mast cells from lung and skin that might explain why adenosine induces a pulmonary but not dermatologic allergy-like response in vivo. In addition, we identify the A3AR as a potentiating receptor of Fc?RI-induced degranulation, thereby implicating it in the in vivo bronchoconstrictive response to adenosine in asthmatics.

SUBMITTER: Gomez G

PROVIDER: S-EPMC3417298 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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Disparity in FcεRI-induced degranulation of primary human lung and skin mast cells exposed to adenosine.

Gomez Gregorio G Zhao Wei W Schwartz Lawrence B LB

Journal of clinical immunology 20110325 3

Inhaled and intravenously administered adenosine induces mast cell-mediated (histamine-dependent) bronchospasm in asthmatics without causing urticaria. A differential response to adenosine by human lung and skin mast cells is shown: low concentrations potentiate FcεRI-induced degranulation of human lung mast cells but not that of skin mast cells. Human lung mast cells were found to express ∼ 3-fold more A3AR messenger RNA (mRNA) than skin mast cells, suggesting the involvement of the G(i)-linked ...[more]

PMID: 21437670

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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

Disparity in Fc?RI-induced degranulation of primary human lung and skin mast cells exposed to adenosine.

Publications

Disparity in FcεRI-induced degranulation of primary human lung and skin mast cells exposed to adenosine.

Similar Datasets

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