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(American Journal of Pathology. 2005;167:1033-1042.)
© 2005 American Society for Investigative Pathology

Bovine Prion Is Endocytosed by Human Enterocytes via the 37 kDa/67 kDa Laminin Receptor

Etienne Morel^*, Thibault Andrieu, Fabrice Casagrande, Sabine Gauczynski, Stefan Weiss, Jacques Grassi, Monique Rousset^*, Dominique Dormont and Jean Chambaz^*

From UMR505 INSERM/Université Pierre et Marie Curie,^* Paris, France; the Service de Neurovirologie, Commissariat à l’Energie Atomique (CEA), Fontenay aux Roses, France; the Service de Pharmacologie et d’Immunologie CEA/Saclay, Gif-sur-Yvette, France; and the Laboratorium für Molekulare Biologie-Genzentrum, Institut für Biochemie der Ludwig-Maximilian Universität München, Munich, Germany

Some forms of transmissible spongiform encephalopathies result from oral infection. We have thus analyzed the early mechanisms that could account for an uptake of infectious prion particles by enterocytes, the major cell population of the intestinal epithelium. Human Caco-2/TC7 enterocytes cultured on microporous filters were incubated with different prion strains and contaminated brain homogenates in the apical compartment. Internalization of infectious particles was analyzed by Western blotting and immunofluorescence. We observed internalization by enterocytes of prion particles from bovine spongiform encephalopathy brain homogenates but not from mouse-adapted scrapie-strain brain homogenates or purified bovine spongiform encephalopathy scrapie-associated fibrils. Bovine prion particles were internalized via endocytosis within minutes of infection and were associated with subapical vesicular structures related to early endosomes. The endocytosis of the infectious bovine PrP^Sc was reduced by preincubating the cells with an anti-LRP/LR blocking antibody, identifying the 37 kDa/67 kDa laminin receptor (LRP/LR), which is apically expressed in Caco-2/TC7 cells, as the receptor for the infectious prion protein. Altogether, our results underscore a potential role of enterocytes in the absorption of bovine prions during oral infection through specific LRP/LR-dependent endocytosis.

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