Diverse patterns of expression of the 67-kD laminin receptor in human small intestinal mucosa: potential binding sites for prion proteins?
It has been shown that the 67-kD laminin receptor (LR) may function as a receptor for Sindbis and tick-born encephalitis viruses. Recent data indicate that the 37-kD precursor (LRP) for this molecule acts as a receptor for prion proteins (PrP), self-proteins implicated in the pathogenesis of transmissible spongiform encephalopathies including new variant Creutzfeldt-Jakob disease (nvCJD). Laminin and PrP share the same binding site on LRP, which is incorporated into the mature LR as a functional binding domain. To localize PrP binding sites potentially relevant to oral infection, the expression of the LR in human small intestinal mucosa was studied. Expression of the LR was determined by immunohistochemistry in duodenal and jejunal biopsies using a monoclonal antibody (MLuC5) which specifically recognizes the 67-kD LR. Biopsy material was obtained from 39 control patients, 15 patients with ulcerative colitis, 15 patients with Crohn's disease and uninvolved small bowel, and 28 patients with active coeliac disease. Two distinctive patterns of LR expression were found within each group of patients. One pattern was characterized by LR expression in the brush border and Golgi apparatus region of villus and crypt enterocytes. Paneth cell secretory granules were positive for LR in these samples. Brush border expression of LR was found in approximately 40% of samples, with the exception of Crohn's disease (6.7% of samples were positive). Another pattern of LR expression was characterized by positively stained endothelium, while the epithelium was generally negative (45 of 97). The use of two polyclonal antibodies which recognize both the LRP and the LR confirmed brush border and paranuclear expression of the LR, but also showed varying cytoplasmic and apical surface immunoreactivity in MLuC5-negative epithelium, reflecting the distribution of LRP as opposed to the mature receptor. In conclusion, expression of the LR in the brush border and in Paneth cell secretory granules suggests that this molecule might be involved in both secretory and endocytotic functions. The major implication of intestinal epithelial/brush border expression of the LR may be an increased susceptibility to oral infection with prion proteins.
Shmakov
A N
AN
Gastrointestinal Laboratory, Department of Medical Sciences, University of Edinburgh, UK.
Bode
J
J
Kilshaw
P J
PJ
Ghosh
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002446:Celiac Disease / Q000378:metabolism*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011328:Prions / Q000378:metabolism*; D017474:Receptors, Laminin / Q000378:metabolism*
D011328:Prions; D017474:Receptors, Laminin