Human mast cell mediators excite neurones in murine and human enteric nervous system

Abstract

Neuroimmune interactions are an integral part of gut pyhsiology and involved in the pathogenesis of inflammatory as well as functional bowel disorders. Mast cells and their mediators are pivotal to communicate information from the innate enteric immune system to the enteric nervous system. So far it is not known whether a mediator cocktail released from activated human mast cells affect neural activity and whether mast cell mediators have effects on human enteric nerves. We used the Multi-Site Optical Recording Technique to image single cell activity in guinea-pig and human enteric nervous system after application of a mast cell mediator cocktail (MCMC) that was released from isolated human intestinal mucosa mast cells stimulated by IgE-receptor crosslinking. We studied 106 nerve cells from 8 human submucous plexus preparations, 64 nerve cells from 9 guinea-pig submucous plexus preparations and 1095 nerve cells from 4 guinea-pig myenteric plexus preparations. Local application of MCMC for 500–100ms onto individual ganglia evoked an excitatory response consisting of action potential discharge. This postsynaptic excitatory response occurred in 31%, 38% or 11% neurons of guinea-pig submucous plexus, human submucous plexus, or guinea-pig myenteric plexus, respectively. Fast excitatory synaptic inputs were not affected by MCMC indicating that MCMC had no presynaptic action. This study revealed for the first time that a mast cell mediator cocktail released from stimulated human intestinal mast cells induces excitatory actions in the human and murine enteric nervous system. We thereby present evidence for the concept that immunoneural signals arising from mast cells are able to enhance activity in the enteric nervous system.