00:01
I've used chemokines,
but haven't explained what they are.
00:03
So here's a quick definition.
00:05
Chemokines, or any
of our variety of proteins
that can recruit and
activate inflammatory,
and even non-inflammatory cells.
00:13
They are expressed by
basically every cell type
that you can think of.
00:16
And there are a whole mess
of chemokines.
00:19
So we're going to give
a little bit more explanation
about those in a minute
because those are
important molecules
in many of the
inflammatory processes.
00:28
Right then, so we have talked about
chemokines.
00:31
They're actually over
50 different kinds of chemokines.
00:34
They live in
four different families.
00:37
They're going to be just two that
we really need to pay attention to,
but there are four families.
00:41
Shown here is the typical structure
of a chemokine.
00:45
It kind of looks like a paperclip.
00:48
In one end is the carboxyl-terminus,
that's the COOH.
00:52
On the other end is the NH2,
that's the amino-terminus.
00:55
And they typically fold
like a paperclip
held together by
two disulfide bonds.
01:00
The disulfide bonds
are between cysteines,
marked here as C's.
01:04
So those are giving you
the disulfide bonds
linking and holding
together the paperclip.
01:10
For CXC chemokine,
there is a preserved motif
of that central cysteine
separated by some other
amino acid,
not otherwise specified,
it's just X,
and then another cysteine.
01:23
So they're called
CXC chemokines.
01:26
So they are important because
as shown in the red box,
they typically recruit neutrophils.
01:32
There are exceptions, but
they typically recruit neutrophils,
and this will show up on boards,
because you'll, they'll ask, with a
CXC chemokine, what does it do?
Recruits neutrophils.
01:42
There is a CC chemokine.
01:44
Same general structure,
same paperclip,
same carboxyl-terminus,
same amino group.
01:49
But instead of having an amino acid
between the two cysteines
there's nothing, it's just CC.
So they're together.
01:57
Same disulfide bonds
holding the paperclip together,
but CC chemokines,
that's slightly different structure
will now typically recruit
only mononuclear cells.
02:07
So we have these two very
important families of chemokines,
and depending on
when they're expressed,
and how they're expressed,
will either recruit neutrophils
or recruit mononuclear
inflammatory cells.
02:19
There are others in the families,
so there is just a single cysteine
and nothing else.
02:24
And then we have cysteine
separated by three amino acids.
02:29
But we're gonna focus on
the CXC and the CC chemokines.
02:33
What are they binding to?
Those chemokines bind 2 receptors.
02:36
And they're pretty impressive
in terms of the complexity,
but they span the membrane
seven times,
and they are linked to G-proteins.
02:44
So there can be
intracellular signaling.
02:46
So the chemokine
will come along,
sit down on top
of the chemokine receptor,
and signal intracellularly.
02:54
The signals,
once that happens,
we'll trigger for example,
changing the integrants
from low affinity to high affinity.
03:03
But chemokines can also drive
just pure cell migration.
03:07
They may be like a whiff of perfume
on the air
that a neutrophil follows on its way
to getting to a particular site.
03:16
So they will drive particular
migration in a direction.
03:20
They may also induce
cellular proliferation,
and they may induce
other cellular activation.
03:26
So chemokines and
chemokine receptors,
do a lot of things.
03:31
We'll come back to review slide
in just a minute
that will put it in context.
03:34
So hang in there.