Prion Interaction with the 37-kDa/67-kDa Laminin Receptor on Enterocytes as a Cellular Model for Intestinal Uptake of Prions |
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Authors: | Dominika Kolodziejczak Bianca Da Costa Dias Chantal Zuber Katarina Jovanovic Julia Beck Vusi Mbazima Bertram Brenig |
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Affiliation: | 1 Laboratorium für Molekulare Biologie, Genzentrum, Institut für Biochemie der LMU, München, Feodor-Lynen-Strasse 25, D-81377 München, Germany2 School of Molecular and Cell Biology, University of the Witwatersrand, Wits 2050, Johannesburg, Republic of South Africa3 Tierärztliches Institut der Universität Göttingen, Burckhardtweg 2, D-37077 Göttingen, Germany4 Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA |
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Abstract: | Enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. We established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kDa/67-kDa laminin receptor LRP/LR. Human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (CWD), scrapie, and bovine spongiform encephalopathy (BSE), respectively. PrPCWD, ovine PrPSc, and PrPBSE all colocalized with LRP/LR on human enterocytes. PrPCWD failed to colocalize with LRP/LR on bovine, porcine, and ovine enterocytes. Ovine PrPSc colocalized with the receptor on bovine enterocytes, but failed to colocalize with LRP/LR on cervid and porcine enterocytes. PrPBSE failed to colocalize with the receptor on cervid and ovine enterocytes. These data suggest possible oral transmissibility of CWD and sheep scrapie to humans and may confirm the oral transmissibility of BSE to humans, resulting in zoonotic variant Creutzfeldt-Jakob disease. CWD might not be transmissible to cattle, pigs, and sheep. Sheep scrapie might have caused BSE, but may not cause transmissible spongiform encephalopathy in cervids and pigs. BSE may not be transmissible to cervids. Our data recommend the enterocyte model system for further investigations of the intestinal pathophysiology of alimentary prion infections. |
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Keywords: | CWD, chronic wasting disease BSE, bovine spongiform encephalopathy TSE, transmissible spongiform encephalopathy PrP, prion protein FACS, fluorescence-activated cell scanning 2D, two-dimensional PBS, phosphate-buffered saline FCS, fetal calf serum DMEM, Dulbecco's modified Eagle's medium P/S, penicillin/streptomycin NEAA, nonessential amino acids |
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