Antigen transport and cytoskeletal characteristics of a distinct enterocyte population in inflammatory bowel diseases.
Intestinal antigen uptake is enhanced in inflammatory bowel disease. We analyzed transcellular transport routes of antigens in different compartments of normal enterocytes and atypical intestinal epithelial cells called "rapid antigen uptake into the cytosol enterocytes" (RACE cells). These cells constitute a recently described population of enterocyte-derived cells, which are increased in inflammatory bowel disease. Mucosa of freshly resected specimens were incubated with the antigens ovalbumin or horseradish peroxidase. Ultrastructural labeling patterns of differentiation-dependent proteins, the brush-border enzyme sucrase-isomaltase and the cytoskeleton proteins villin and actin, were determined in enterocytes. Apoptosis was investigated biochemically and ultrastructurally by cleavage of caspase-3. Both antigens were transported to late endosomes and to trans-Golgi vesicles of enterocytes in inflammatory bowel disease and control specimens. Quantitative evaluation revealed a significantly increased transepithelial antigen transport in both compartments of RACE relative to normal enterocytes. Labeling densities for sucrase-isomaltase, villin, and actin were decreased in RACE relative to normal enterocytes. Caspase-3 was not increased in RACE cells relative to controls. RACE cells are characterized by increased antigen transport to late endosomes and the trans-Golgi network, a disassembled cytoskeleton and lower concentrations of proteins that are markers of cell differentiation.
Department of Pediatrics, University of Muenster, Albert-Schweitzer-Str. 33, 48149 Muenster, Germany. zimmerp@uni-muenster.de.
Sabine
S
Kersting
Matthias
M
Bruewer
Guido
G
Schuermann
Axel
A
Klotz
Markus
M
Utech
Matthias
M
Hansmerten
Christian F
CF
Krieglstein
Norbert
N
Senninger
Joerg-Dieter
JD
Schulzke
Hassan Y
HY
Naim
Klaus-Peter
KP
Zimmer
D000199:Actins / Q000378:metabolism; D000328:Adult; D000941:Antigens / Q000378:metabolism*; D017209:Apoptosis; D002352:Carrier Proteins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism* / Q000473:pathology; D011992:Endosomes / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006735:Horseradish Peroxidase / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000502:physiology*; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D010047:Ovalbumin / Q000378:metabolism*; D021381:Protein Transport; D013394:Sucrase-Isomaltase Complex / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
D000199:Actins; D000941:Antigens; D002352:Carrier Proteins; D008840:Microfilament Proteins; C026615:villin; D010047:Ovalbumin; D006735:Horseradish Peroxidase; D013394:Sucrase-Isomaltase Complex; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases