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Hello.
My name is Tracy Hussell.
I am currently the Director of
the Manchester Collaborative
Centre for Inflammation Research.
I'm also a professor
of inflammatory disease
at the University of Manchester
in the United Kingdom.
My email address is shown
at the bottom of this slide
should you want to speak with me.
And today I'm going to talk
about airway macrophages
in health and disease.
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My group has been working
for a number of years
now on the regulation of airway
macrophages in health, how
that regulation is lost during
an inflammatory condition,
and the altered state that it ends
up in upon inflammatory resolution.
And we believe that
all of these changes
are dictated by the
respiratory epithelium.
So the respiratory
epithelium, when it is intact,
provides a number of
negative regulatory signals
that raise the threshold above
which an airway macrophage will
become activated.
So, for example, the
respiratory epithelium
secretes surfactant proteins, shown
by the red and yellow star, which
will bind to receptors such as the
one shown here, SIRP alpha.
And that transmits a
negative regulatory signal
to the airway macrophage.
The respiratory epithelium can also
activate transforming growth factor
beta via the expression of
that beta six integrins.
And this combination also provides
a negative regulatory signal
to airway macrophages.
Mucins secreted and expressed
on the luminal aspect
of the respiratory epithelium
are also immune-suppressive,
as is the expression of high levels
of the immunoglobulin receptor
CD200 that binds to CD200
receptors on airway macrophages.
So as you can see
from this slide, there
are a number of things
provided by or expressed
by the respiratory epithelium that
raise the threshold above which
an airway macrophage
can become activated.
Now, it's likely that polymorphisms
exist in all of these things
that I've shown you here, which
means that we will all have
a slightly different
state above which
our airway macrophages
will become activated.
We feel that these concepts are
relevant to multiple inflammatory
conditions, and it gives us a
different concept, in a way,
in that it's not just antigen that
drives an inflammatory response,
it's an antigen that
is sufficient enough
to disrupt the
respiratory epithelium.
So for inflammation to proceed
in the respiratory tract,
we need an antigen and we also need
a loss of epithelium, which will
take away the
regulation that normally
controls airway macrophages.
All of the concepts
that I'm dealing with
are relevant to all of
these following conditions:
asthma, COPD, idiopathic pulmonary
fibrosis, cystic fibrosis, lung
cancer, bronchitis, bronchiectasis,
pneumonia, and infection.
And this concept is what I'm
going to talk about in the rest
off my lecture today.
