Project Details
Projekt
Mast cell - nerve interactions in the human intestine
Applicant
Professor Dr. Michael Schemann
Subject Area
Dermatology
Term
from 2012 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 222082822
Close anatomical association between nerves and mast cells in the gut wall suggest that interactions between the two systems influence gut functions in health and disease. Such interactions, however, have never been demonstrated at a cellular level in intact tissue. The aim of the project is to investigate nerve - mast cell cross talk in the human intestine using Ca imaging as a reporter for cell activation. We will record nerve responses after mast cell specific activation with IgE receptor cross linking. In addition we analyze mast cell activation after electrical stimulation of nerves. In this way we simultaneously record mast cell and nerve activity in order to detect for the first time communication between them in intact tissue. Specificity of the mast cell to nerve signaling or nerve to mast cell signaling will be shown by the sensitivity of the nerve response to histamine receptor antagonists or the sensitivity of mast cell responses to CGRP and SP antagonists, respectively. Apposition between mast cells and nerves is confirmed by immunohistochemical labeling and correlated to their Ca signals. Signaling pathways between mast cells and nerves will be mapped by following the mast cell or nerve triggered activation of nerve processes. The results will provide the first direct evidence for mast cell nerve signaling in the human gut. The novel insights advance our knowledge of how the mast cell nerve axis integrates physiological signals and help to better target gut symptoms under conditions of sensitized mast cell nerve signaling.
DFG Programme
Priority Programmes
