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Characterization of M cell development during indomethacin-induced ileitis in rats
T Kucharzik1, A Lügering, N Lügering
1Department of Medicine B, University of Münster, Münster, Germany.
Background:
M cells play an important role in the intestinal immune system as they have a high capacity for transcytosis of a wide range of microorganisms and macromolecules. However, little is known about the role of M cells during intestinal inflammation.
Aim:
We studied M cell development during indomethacin-induced intestinal inflammation in rats.
Methods:
Ileitis in rats was induced by two subcutaneous injections with indomethacin (7.5 mg/kg) given 24 h apart. Rats were sacrificed after 14 days and tissue was analysed by fluorescence microscopy and electron microscopy. M cells could be visualized by using the FITC-labelled mAb anti-cytokeratin (CK)-8 (clone 4.1.18), which was recently identified as specific M cell marker in rats. The number of cytokeratin-8 positive M cells was related to the surface of the follicle associated epithelium. For morphological studies, we used both transmission electron microscopy (T.E.M.) and scanning electron microscopy (S.E.M.).
Results:
In non-inflamed ileum M cells were scarce. Only 4% of the follicle associated epithelium were M cells, whereas an increase of M cells up to 11% was found in inflamed follicle associated epithelium (P < 0.001). The rate of M cell induction depended on the macroscopic degree of inflammation. T.E.M./S.E.M. studies showed that in inflamed tissue most M cells underwent apoptosis with typical morphological signs. In contrast to apoptotic M cells, the neighbouring enterocytes usually appeared intact. The number of mononuclear cells below the follicle associated epithelium was significantly increased. S.E.M. studies revealed that during induced ileitis mononuclear cells migrated from the lamina propria into the gut lumen by passing through apoptotic M cells.
Conclusions:
During indomethacin-induced ileitis in rats the increase in M cell number in association with apoptosis of M cells may alter the intestinal barrier function. These observations may play a pivotal role in the pathogenesis of chronic intestinal inflammation, e.g. in inflammatory bowel disease.
Insights
During intestinal inflammation, M cells increase and undergo apoptosis, potentially altering gut barrier function. This finding is crucial for understanding chronic inflammatory diseases like inflammatory bowel disease.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- M cells are key players in the intestinal immune system, facilitating the transport of substances across the gut lining.
- Their role during intestinal inflammation remains largely unknown.
Purpose of the Study:
- To investigate M cell development and behavior during indomethacin-induced intestinal inflammation in rats.
Main Methods:
- Ileitis was induced in rats using indomethacin injections.
- Tissue analysis involved fluorescence microscopy and transmission/scanning electron microscopy (T.E.M./S.E.M.).
- M cells were identified using a specific rat M cell marker, anti-cytokeratin (CK)-8.
Main Results:
- M cells were significantly increased in inflamed ileum (11%) compared to non-inflamed tissue (4%).
- Electron microscopy revealed M cells undergoing apoptosis in inflamed areas, while enterocytes remained intact.
- Mononuclear cells migrated from the lamina propria into the gut lumen through apoptotic M cells.
Conclusions:
- Increased M cells and their apoptosis during ileitis may compromise intestinal barrier function.
- These changes could be pivotal in the pathogenesis of chronic intestinal inflammation, including inflammatory bowel disease.