Abstract
Introduction: It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. We aimed to record for the first time signaling between mast cells and neurons in intact human submucous preparations.Methods: We used the Ca2+ sensitive dye Fluo-4 AM to simultaneously image changes in intracellular calcium [Ca+2]i (%ΔF/F) in neurons and mast cells. Data are presented as median with interquartile ranges (25/75%).Results: We recorded nerve responses in 29 samples upon selective activation of 223 mast cells by IgE receptor cross linking with the antibody mAb22E7. Mast cells responded to mAb22E7 with a median [Ca+2]i increase of 20% (11/39) peaking 90 s (64/144) after the application. Only very few neurons responded and the median percentage of responding neuronal area was 0% (0/5.9). Mast cell activation remained in the presence of the fast sodium channel blocker tetrodotoxin. Specific neuronal activation by transmural electrical field stimulation (EFS) in 34 samples evoked instantaneously [Ca+2]i signals in submucous neurons. This was followed by a [Ca+2]i peak response of 8%ΔF/F (4/15) in 33% of 168 mast cells in the field of view. The mast cell response was abolished by the nerve blocker tetrododoxin, reduced by the Calcitonin Gene-Related Peptide receptor 1 antagonist BIBN-4096 and the Vasoactive Intestinal Peptide receptor antagonist PG97-269, but not by blockade of the neurokinin receptors 1–3.Conclusion: The findings revealed bidirectional signaling between mast cells and submucous neurons in human gut. In our macroscopically normal preparations a nerve to mast cell signaling was very prominent whereas a mast cell to nerve signaling was rather rare.
Highlights
It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis
We previously demonstrated that the mast cell mediators histamine and tryptase as well as a mediator cocktail release from human intestinal mast cells upon IgE receptor crosslinking by mAb22E7 activated human submucous neurons (Schemann et al, 2005; Breunig et al, 2007; Ostertag et al, 2017)
The overall goal of the present project was to study nerve-mast cells (MCs) signaling in submucous plexus preparations from human intestine
Summary
It is suggested that an altered microenvironment in the gut wall alters communication along a mast cell nerve axis. It is the largest immune competent organ in our body and it harvests an enormous number of nerves. Most of the nerve structures belong to the enteric nervous system (ENS) which regulates gut functions autonomously. The remaining extrinsic nerves connect the central nervous system with the gut and belong either to the afferent gut-brain or the efferent brain-gut axis. Both the sensory as well as the motor pathways ramify extensively once entering the gut wall. The ENS consists of two ganglionated plexus: the myenteric plexus between the two
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
