Comparison of Cattle and Sheep Colonic Permeabilities to Horseradish Peroxidase and Hamster Scrapie Prion Protein in Vitro

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 of (125)I-labelled inactivated Syrian hamster scrapie prion protein (ShaPrP(sc)) 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 = P(o). exp(-K.ra). The "ideal" permeabilities, P(o) 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.