Inflammatory Chemokines

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.