Altered interaction between enteric glial cells and mast cells in the colon of women with irritable bowel syndrome

Neurogastroenterol Motil. 2021 Nov;33(11):e14130. doi: 10.1111/nmo.14130. Epub 2021 Apr 2.

Felipe Meira de-Faria 1, Maite Casado-Bedmar 1, Carl Mårten Lindqvist 2, Michael P Jones 3, Susanna A Walter 1 4, Åsa V Keita 1


Author information

1Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.

2Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.

3Macquarie University, Sydney, New South Wales, Australia.

4Department of Gastroenterology, Linköping University, Linköping, Sweden.


Background: Enteric glial cells (EGC) and mast cells (MC) are intimately associated with gastrointestinal physiological functions. We aimed to investigate EGC-MC interaction in irritable bowel syndrome (IBS), a gut-brain disorder linked to increased intestinal permeability, and MC.

Methods: Parallel approaches were used to quantify EGC markers in colonic biopsies from healthy controls (HC) and patients with IBS. Data were correlated with MC, vasoactive intestinal polypeptide (VIP) and VIP receptors (VPAC1/VPAC2) expressions, and bacterial translocation through biopsies mounted in Ussing chambers. In addition, we investigated the effects of EGC mediators on colonic permeability and the pharmacological-induced responses of EGC and MC cell lines.

Key results: Immunofluorescence of IBS colonic mucosa, as well as Western blotting and ELISA of IBS biopsy lysates, revealed increased glial fibrillary intermediate filament (GFAP) expression, indicating EGC activation. Mucosal GFAP correlated with increased MC and VPAC1+ MC numbers and decreased VIP+ MC, which seemed to control bacterial translocation in HC. In the contrary, EGC activation in IBS correlated with less MC and VPAC1+ MC numbers, and more VIP+ MC. In vitro, MC and EGC cell lines showed intracellular calcium responses to each other's mediators. Furthermore, EGC mediators prevented VIP-induced MC degranulation, while MC mediators induced a reactive EGC phenotype. In Ussing chambers, EGC mediators decreased paracellular passage through healthy colonic biopsies.

Conclusions & inferences: Findings suggest the involvement of EGC and MC in the control of barrier function in the human colon and indicate a potential EGC-MC interaction that seems altered in IBS, with detrimental consequences to colonic permeability. Altogether, results suggest that imbalanced EGC-MC communication contributes to the pathophysiology of IBS.

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