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Division of
Biomedical Sciences (Physiology Group), King's College, London, UK
Correspondence to: 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
Accepted for publication 2 June 1999
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
125I-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.
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