Functional interaction of cultured mucosal mast cells and isolated enteric neurons in mice

      We have already reported that CGRP-immunoreactive intrinsic sensory nerve fibers specifically increase in the colonic mucosa of food allergy (FA) model mice. Furthermore, in our previous studies, mucosal mast cells (MMCs) are increased and juxtaposed with CGRP-positive enteric nerve fibers in the colonic mucosa of FA mice. We investigated the functional interaction between MMCs and enteric neurons using a co-culture system of bone marrow-derived mast cells (BMMCs) and isolated enteric neurons to mimic the pathophysiological state of the intestine in FA condition. Mucosal type BMMCs (mBMMCs) were prepared from BALB/c mice using SCF, IL-3, IL-9 and TGF-β. Enteric neurons were isolated from the small intestine of BALB/c mice. The activation of isolated enteric neurons and mBMMCs was analyzed with calcium imaging technique. Stimulation of mBMMCs with IgE-DNP in the co-culture condition produced an elevation of intracellular calcium concentration ([Ca2+]i) in the isolated enteric neurons, which reached approximately 65% of that of treatment with a calcium ionophore A23187. On the other hand, activation of the isolated enteric neurons with Na + channel activator veratridine, which can stimulate only neurons, in the co-culture condition, led to an increase in [Ca2+]i in mBMMCs, which reached approximately 57% of that of treatment with A23187. Our data suggest that the interaction between mucosal mast cells and enteric neurons may be involved in the pathogenesis of FA.
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