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Comparison of cattle and sheep colonic permeabilities to horseradish peroxidase and hamster scrapie prion protein in vitro
  1. A T McKie,
  2. P S Zammit,
  3. R J Naftalin
  1. Division of Biomedical Sciences (Physiology Group), King's College, London, UK
  1. Dr R J Naftalin, Division of Biomedical Sciences (Physiology Group), King's College London, Guy's Campus, London SE1 1UL, UK. Email:richard.naftalin{at}kcl.ac.uk

Abstract

BACKGROUND Paracellular permeability to solutes across the descending colon is much higher in cattle than sheep. This is a possible route for transmission of infective materials, such as scrapie prion.

AIMS To compare the permeabilities of labelled scrapie prion protein and other macromolecules in bovine and ovine descending colons in vitro.

METHODS Using fresh slaughterhouse material, transepithelial fluxes of macromolecules across colonic mucosae mounted in Ussing chambers were measured by monitoring transport of either enzyme activity or radioactivity.

RESULTS The comparative bovine to ovine permeability ratio of the probes increased with molecular weight: from 3.1 (0.13) for PEG400 to 10.67 (0.20) (p<0.001) for PEG4000; and from 1.64 (0.17) for microperoxidase to 7.03 (0.20) (p<0.001) for horseradish peroxidase (HRP). The permeability of125I-labelled inactivated Syrian hamster scrapie prion protein (ShaPrPsc) was 7.02 (0.33)-fold higher in bovine than ovine colon (p<0.0025). In each species, the probe permeabilities decreased according to the formula: P = Po.exp(−K.ra). The “ideal” permeabilities, Po are similar, however, K(ovine) = 2.46 (0.20) cm/h/nm exceeds K(bovine) = 0.85 (0.15) cm/h/nm (p<0.001) indicating that bovine colon has a higher proportion of wide pores than ovine. Image analysis confirmed that HRP permeated through the bovine mucosal layer via a pericryptal paracellular route much more rapidly than in sheep.

CONCLUSIONS These data may imply that scrapie prion is transmitted in vivo more easily across the low resistance bovine colonic barrier than in other species.

  • cattle
  • sheep
  • colon
  • paracellular permeability
  • horseradish peroxidase
  • hamster scrapie prion protein
  • Abbreviations used in this paper

    BSE
    bovine spongiform encephalitis
    DAB
    3,3′-diamino-benzidine tetrahydrochloride
    HRP
    horseradish peroxidase
    MBM
    meat and bone meal
    MS
    mucosal to serosal
    PEG
    polyethylene glycol
    PrPsc
    scrapie prion protein
    ShaPrPsc
    Syrian hamster scrapie prion protein
    SM
    serosal to mucosal
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  • Abbreviations used in this paper

    BSE
    bovine spongiform encephalitis
    DAB
    3,3′-diamino-benzidine tetrahydrochloride
    HRP
    horseradish peroxidase
    MBM
    meat and bone meal
    MS
    mucosal to serosal
    PEG
    polyethylene glycol
    PrPsc
    scrapie prion protein
    ShaPrPsc
    Syrian hamster scrapie prion protein
    SM
    serosal to mucosal
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