Intestinal tissue distribution and epithelial transport of the oral immunogen LTB, the B subunit of E. coli heat-labile enterotoxin.
LTB provokes a systemic immune response and exerts adjuvant effects on mucosal immune responses to unrelated antigens. The binding and uptake of fluorescein-labelled LTB in the normal villus epithelium was compared to that in Peyer's patch dome epithelium in mouse intestine. LTB was bound by the GM1-receptor and taken up extensively by both tissues, indicating that not only the Peyer's patches but also the normal villus epithelium play a significant role in the transport of orally administered antigens. These results were supported by transport studies in the human intestinal epithelial cell line Caco-2 using 125I-LTB. After 2 h incubation, 5.1 +/- 0.1% and 5.9 +/- 0.1% of the added radioactivity was transported in the apical to basolateral and basolateral to apical direction, respectively. Less than 1% of the transported radioactivity was immunoprecipitated with anti-LTB antiserum indicating that LTB was extensively degraded during the transport. The results suggest that normal enterocytes play a significant role in the binding, uptake and transport of orally administered LTB.
Lazorová
L
L
Uppsala University, Department of Pharmaceutics, Sweden.
Sjölander
A
A
Russell-Jones
G J
GJ
Linder
J
J
Artursson
P
P
D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000493:pharmacokinetics* / Q000494:pharmacology; D002277:Carcinoma / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology / Q000493:pharmacokinetics* / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D010581:Peyer's Patches / Q000378:metabolism; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli; D016650:Fluorescein-5-isothiocyanate