Transcripts
DR. LINGWOOD:
What we've done here is to take
human renal endothelial cells and treat them with a substance
called tumor necrosis factor (TNF) or LPS. LPS
is the sugar polymer that coats bacteria and is a
virulence factor in an infection.
And here if you treat with TNF
and then measure the cell sensitivity to
verotoxin you see increased sensitivity - cells
get killed and the amount of Gb3 goes up. So
the cytokines somehow deliver a signal to the
cell to make Gb3.
Why, we don't know, but, of
course, in terms of an infection that would be
bad news because now the cells in the glomerulus
could be stimulated to make Gb3 and will
therefore become sensitive to verotoxin. The
same thing is true with LPS.
Now, normally when you get an
infection, the LPS will not raise the serum
cytokines. But as you get older, your immune
system wanes in its regulations. So what we
propose is that in the elderly there is an
abnormal cytokine response. Thus other factors
of the infection, that is the LPS of the
bacterium during the infection, induce a time
dependent stimulation of Gb3 synthesis in the
microvasculature endothelial cells of the
glomerulus of the elderly, and then those cells
are now set up to become sensitive to verotoxin
leading to HUS.
You and I, we don't make --
well, maybe I'm getting nearer the age where I
might -- but you and I don't usually make a
high cytokine response in response to infection.
So that's why we don't stimulate Gb3 synthesis
in our kidney.
However, in baboons some studies
by Siegler at Salt Lake City show clearly that
verotoxin on its own, with no cytokine
stimulation, will induce HUS.
