Chemokines

Chemoattractant cytokines (Chemokines) are a superfamily of small polypeptides that selectively control the adhesion, chemotaxis and activation of many type of leukocyte populations. Chemokines are chemoattractant cytokines that regulate the selective migration of leukocytes through binding to specific chemokine receptors differentially expressed on various leukocyte populations. So called "housekeeping" chemokines are produced in lymphoid organs and tissues or in non-lymphoid sites like skin where they direct normal trafficking of lymphocytes such as determining the correct positioning of leukocytes generated by hematopoiesis. About 50 chemokines and 20 chemokine receptors have been identified in human.

Inflammatory chemokines are typically induced in response to infection. Chemokines cause leukocytes to move into various tissue sites by inducing the adherence of these cells to the vascular endothelium.

Functions of Chemokines

The Various classes of Chemokines

Signal Transduction; Chemokines and their receptors

Chemokines deliver signals through seven-transmembrane-spaning receptors. Chemokine action is mediated by receptors whose polypeptide chain traverses the membrane seven times. When a receptor binds an appropriate chemokine, it activates heterotrimeric large G proteins, initiating a signal transduction process that generates second messengers like cAMP, IP3, Ca2+, and activated small G proteins. This promotes greater adhesiveness by activation of leukocyte integrins and the generationof microbicidal oxygen radicals in phagocytes.

Chemokine Receptors   

Dendritic Cells and Chemokines

Chemokines and Chemokine Receptors as Th1/TH2 Defining Factors

Chemokines and Disease

--HIV

Chemokines and their receptors play a central role in HIV infection and disease progression. In order to gain entrance into its traget cells, HIV must interact with CD4 and a second receptor or co-receptor belonging to the chemokine receptor family, either CCR5 or CSCR4. This discovery was made after the demonstration of the anti-HIV activity of three chemokines that were later demonstrated to bind to CCR5.

--Th1/Th2-type diseases

In multiple sclerosis and rheumatoid arthritis, which are Th1-related diseases, CCR5+ and CXCR3+ T cells are accumulated, and their ligands, CCL3 (MIP)-1alpha and IP-10 are detected at inflammatory sites. On the other hand, a higher expression of TARC is detected on Reed-Sternberg cells of Hodgkin's lymphoma that have the characteristic feature of infiltration of Th2.