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 re ceptor for Sindbis and tick-born encephalitis viruses, Recent data indicate that the 37-kD precursor (LRP) for this molecule acts as a receptor for pr ion proteins (PrP), self-proteins implicated in the pathogenesis of transmi ssible 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 local ize PrP binding sites potentially relevant to oral infection, the expressio n 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-k D LR, Biopsy material was obtained from 39 control patients, 15 patients wi th ulcerative colitis, 15 patients with Crohn's disease and uninvolved smal l bowel, and 28 patients with active coeliac disease, Two distinctive patte rns 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 tvas characte rized 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 o f the LR, but also shelved varying cytoplasmic and apical surface immunorea ctivity 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 mole cule might be involved in both secretory and endocytotic functions. The maj or implication of intestinal epithelial/brush border expression of the LR m ay be an increased susceptibility to oral infection with prion proteins. Co pyright (C) 2000 John Wiley & Sons, Ltd.