Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection
العنوان: | Mannitol triggers mast cell-dependent contractions of human small bronchi and prostacyclin bronchoprotection |
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المؤلفون: | Sven-Erik Dahlén, Ann-Charlotte Orre, Johan Raud, Mamdoh Al-Ameri, Johan Bood, Mikael Adner, Martijn L. Manson, Jesper Säfholm |
المصدر: | Journal of Allergy and Clinical Immunology, 144(4), 984-992 Journal of Allergy and Clinical Immunology |
سنة النشر: | 2019 |
مصطلحات موضوعية: | 0301 basic medicine, medicine.drug_class, Bronchoconstriction, Immunology, Prostacyclin, Bronchi, Pharmacology, Receptors, Epoprostenol, Bronchial Provocation Tests, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Organ Culture Techniques, medicine, Immunology and Allergy, Humans, Mannitol, Mast cell stabilizer, Mast Cells, Prostacyclin receptor, Leukotriene, Chemistry, Muscle, Smooth, Mast cell, Epoprostenol, Asthma, Exercise-Induced, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Prostaglandin D2, medicine.symptom, Histamine, medicine.drug, Muscle Contraction |
الوصف: | BACKGROUND:Clinical research supports that exercise-induced bronchoconstriction (EIB) is caused by hyperosmolar triggering of mast cells. The reaction can be mimicked by inhalation of mannitol, but it has paradoxically previously not been possible to replicate this mode of action of mannitol in isolated airways. OBJECTIVE:We sought to establish an ex vivo model of EIB in human small bronchi. METHODS:Small bronchi (inner diameter, 0.5-2 mm) from macroscopically healthy human lung tissue were obtained from 48 patients and mounted in organ baths. Contractions and mediator release were analyzed after challenge with hyperosmolar mannitol (850 mOsm). RESULTS:Ten minutes of exposure to mannitol caused a small initial contraction (12% ± 1% of maximum) that was followed by a second and much larger contraction (maximum effect [Emax], 47% ± 5%) when mannitol was washed out. The mast cell stabilizer cromolyn reduced the second contraction (Emax, 27% ± 3%). Furthermore, this main contraction was abolished by the combination of antagonists of histamine and cysteinyl leukotrienes in the presence of indomethacin. Mannitol increased the release of the mast cell mediators histamine (9.0-fold), cysteinyl leukotrienes (4.5-fold), and prostaglandin (PG) D2 (5.4-fold), as well as PGE2 (6.3-fold) and the prostacyclin metabolite 6-keto PGF1α (5.7-fold). In contrast, indomethacin alone enhanced the bronchoconstriction (Emax, 68% ± 6%). Likewise, receptor antagonists for PGE2 (EP2 and EP4) and prostacyclin (IP) also enhanced the mannitol-induced bronchoconstriction (Emax, 67% ± 5%, 66% ± 4%, and 68% ± 3%, respectively). In bronchi precontracted by carbachol, the IP receptor agonist cicaprost induced profound relaxation. CONCLUSION:This new protocol established an in vitro model for studies of EIB in isolated human bronchi. The IP receptor might be a new target for asthma treatment. |
اللغة: | English |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d8023c18fc18610624a75010c9139e90 http://hdl.handle.net/1887/138269 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....d8023c18fc18610624a75010c9139e90 |
قاعدة البيانات: | OpenAIRE |
الوصف غير متاح. |