title: CGRP, a neurotransmitter of enteric sensory neurons, contributes to the development of food allergy due to the augmentation of microtubule reorganization in mucosal mast cells.
abstract: Neuro-immune interaction in the gut is substantially involved in the maintenance of intestinal immune homeostasis and the pathology of intestinal immune diseases. We have previously demonstrated that mucosal mast cells and nerve fibers containing CGRP, a neurotransmitter of intrinsic enteric sensory neurons, are markedly increased and exist in close proximity to each other in the colon of food allergy (FA) mice. In the present study, a CGRP-receptor antagonist BIBN4096BS significantly alleviated allergic symptoms in the murine FA model. In addition, the elevated numbers of mucosal mast cells in the proximal colon of FA mice were significantly decreased in that of BIBN4096BS-treated FA mice. Thus, we investigated the effects of CGRP on calcium-independent process in degranulation of mucosal mast cells since CGRP increases intracellular cAMP levels, but not Ca(2+) concentration. CGRP did not alter a calcium ionophore A23187-increased cytosolic Ca(2+) concentration in mucosal-type bone marrow-derived mast cells (mBMMCs), but did augment microtubule reorganization in resting and A23187-activated mBMMCs. Furthermore, CGRP alone failed to cause the degranulation of mBMMCs, but CGRP significantly enhanced the degranulation of mBMMCs induced by A23187. Together, these data indicate that CGRP- enhanced microtubule reorganization augments IgE-independent/non-antigenic stimuli-induced mucosal mast cell degranulation, thereby contributing to the development of FA.
authors.affiliation: Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Jaemin
authors.initials: J
authors.lastname: Lee
authors.forename: Tomoe
authors.initials: T
authors.lastname: Yashiro
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hamada
authors.forename: Shusaku
authors.initials: S
authors.lastname: Hayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kadowaki
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003967:Diarrhea / Q000188:drug therapy; D004195:Disease Models, Animal; D005512:Food Hypersensitivity / Q000276:immunology* / Q000628:therapy; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism*; D008415:Mastocytosis / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000276:immunology*; D010047:Ovalbumin / Q000009:adverse effects; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000276:immunology*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018377:Neurotransmitter Agents; D010879:Piperazines; D011799:Quinazolines; D010047:Ovalbumin; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant