Characterization of M cell development during indomethacin-induced ileitis in rats.
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.


OBJECTIVE
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.
Kucharzik
T
T
Department of Medicine B, University of Münster, Münster, Germany.
Lügering
A
A
Lügering
N
N
Rautenberg
K
K
Linnepe
M
M
Cichon
C
C
Reichelt
R
R
Stoll
R
R
Schmidt
M A
MA
Domschke
W
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D007079:Ileitis / Q000139:chemically induced / Q000473:pathology*; D007120:Immunochemistry; D066298:In Vitro Techniques; D007213:Indomethacin; D007633:Keratins / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010581:Peyer's Patches / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D007633:Keratins; D016650:Fluorescein-5-isothiocyanate; D007213:Indomethacin