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 transmis sion of infective materials, such as scrapie prion. Aims-To compare the permeabilities of labelled scrapie prion protein and ot her macromolecules in bovine and ovine descending colons in vitro. Methods-Using fresh slaughterhouse material, transepithelial fluxes of macr omolecules 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 in creased 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 (0.2 0) (p<0.001) for horseradish peroxidase (HRIS). The permeability of I-125-l abelled 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 speci es, the probe permeabilities decreased according to the formula: P = P-o.ex p(-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) ind icating that bovine colon has a higher proportion of wide pores than ovine. Image analysis confirmed that HRP permeated through the bovine mucosal lay er 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.