Chemokines – Lymphocyte Recirculation and Homing

00:01 Chemokines can be grouped into four different family.

00:06 They are essentially chemotactic cytokines.

00:10 But that’s not the only thing they do, they don’t just act as chemotactic factors, they have multiple other effects as well.

00:18 The four families are defined based upon the arrangement of cysteine amino acids in their structure.

00:27 So the C family chemokines just have a single cysteine that forms a disulphide bond.

00:35 And there are quite a few members of this family.

00:39 One example is a chemokine called lymphotactin or XCL1, to give it its alternative name.

00:49 The CC family of chemokines have two cysteine residues that are next to each other.

00:57 So two adjacent cysteine residues.

01:00 And an example of a CC family chemokine is RANTES or CCL5.

01:09 CXC family chemokines have two cysteines that are separated by a single amino acid.

01:15 It really doesn’t matter which amino acid that is.

01:17 It can be any amino acid, that’s what the X represents here, that they have a cysteine, then another amino acid, and then a cysteine; CXC family chemokines.

01:27 An example of a CXC family chemokine is interleukin-8.

01:33 Interluekin-8 is a member of the interleukin cytokines that has chemotactic activity.

01:39 It can also be designated as CXCL8.

01:45 And then finally, the fourth member of the chemokine family is the CX3C family.

01:52 And here, you probably guess by now, they have a cysteine, then three amino acids, can be any three amino acids; and then another cysteine.

02:03 So two cysteines separated by three amino acids.

02:07 An example of a CX3C family chemokine is fractalkine or CX3CL1.

02:17 Chemokines form a chemotactic gradient.

02:21 So they’ll be produced in response to a stimulus.

02:25 And the place where they’re being produced, they’ll be at their highest concentration.

02:30 And then further away from that location, the concentration will decrease.

02:34 So the lymphocytes move on the concentration gradient.

02:39 In order to do that, they need to detect the presence of a chemokine.

02:44 So they have chemokine receptors on their surface.

02:49 And the chemokine receptors are typically members of a 7-transmembrane receptor family that are linked to G-proteins.

03:00 So they have a rather convoluted transmembrane sequence that passes through the cell surface membrane seven times.

03:07 And just underlying the cell membrane is a G-protein consisting of three units - alpha (α), beta (β) and gamma (γ).

03:16 And when the chemokine binds to its receptor, a signaling event is initiated leading to cell activation and migration of the cells up the chemokine gradient.