Transcripts
DR. LINGWOOD:
Okay. So what
we're saying, then, is in the kidney, in the
pediatric population, the blood vessels within
the glomerulus, (and actually there's mesangial
cells, too, they are also positive) - they
express the receptor and then disappear for some
reason during development. I will tell you what
I think the reason is later.
But the renal tubules express
the toxin receptor throughout life, but not every
tubule. As you saw, some tubules do and some
don't. And this is similar to animal models.
People have been spending a lot of time trying
to get an animal model of HUS and they have failed.
And the reason is because Gb3,
the receptor, is not expressed in the glomerulus
of, as far as I know, any other animal, except
maybe monkeys and primates, which are very
expensive. So in the standard model of diseased
rabbits, rats, guinea pigs, what have you, Gb3
is again expressed in the tubules but not in the
glomerules.
And what you get if you treat
animals with verotoxin is tubular necrosis which
is also seen in the worst cases of HUS. So
the primary target in man is probably the renal
glomerulus, but the tubules are involved at a
later stage because they also express the
receptor.
Now, the problem, of course, is
that the elderly also can get HUS following VTEC
infection, but they don't have the receptors that
are in their glomeruli. I've shown you that.
So what is the explanation
there? And the explanation I believe is that
cytokines can induce the expression of the
receptor. Cytokines are molecules produced by
endothelial cells or by monocytes.
