Abstract
We recently identified mucosal mast cell and eosinophil hyperplasia in association with a duodenal impaired barrier function in functional dyspepsia (FD). We aimed to further describe the implication of these immune cells by assessing their activation state at the ultrastructural level and by evaluating the association between impaired epithelial integrity and immune activation. Duodenal biopsies were obtained from 24 FD patients and 37 healthy controls. The ultrastructure of mast cells and eosinophils was analyzed by transmission electron microscopy. Transepithelial electrical resistance and paracellular permeability were measured to evaluate epithelial barrier function. The type of degranulation in eosinophils and mast cells was piecemeal. Eosinophils displayed higher degree of degranulation in FD patients than in controls (p < 0.0001). Quantification revealed a decreased granular density in eosinophils of FD patients (p < 0.0001). The degree of degranulation in mast cells was similar in both groups. However, a more heterogeneous profile was found in the FD group (p < 0.0001). No association between epithelial integrity and the number and activation state of mucosal eosinophils and mast cells was found. We demonstrated ultrastructural changes in degranulation state of eosinophils and mast cells, suggesting that eosinophil and mast cell activation play a role in the pathophysiology of FD.
Highlights
The continuously increasing number of studies reporting low-grade duodenal inflammation in functional dyspepsia (FD) were mainly based on the histological detection of a slightly but significant increased number of mucosal immune cells, mainly eosinophils and mast cells[4]
The results show an increased number of both eosinophils (179.6 ± 15.0 vs. 241.5 ± 14.0 major basic protein (MBP) + cells/mm[2], p = 0.007) (Fig. 1A,B) and mast cells (268.7 ± 20.7 vs. 390.6 ± 20.7 tryptase + cells/mm[2], p = 0.0003) (Fig. 1C,D) in patients with FD compared with control samples
For the first time, mucosal immune activation by identifying marked eosinophil degranulation and a more heterogeneous granule content of mast cells in patients with FD compared with healthy controls
Summary
The continuously increasing number of studies reporting low-grade duodenal inflammation in FD were mainly based on the histological detection of a slightly but significant increased number of mucosal immune cells, mainly eosinophils and mast cells[4]. We demonstrated increased duodenal permeability in patients with FD and found a correlation between certain cell-to-cell adhesion proteins and low-grade inflammation[8]. These data indicate that there is an association between impaired integrity and inflammatory activity, we do not know whether increased permeability is the cause or consequence of low-grade inflammation or even an unrelated www.nature.com/scientificreports/. We wanted to investigate the relationship between impaired integrity and eosinophil and mast cell activation in FD patients
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