*This table lists most known chemokine receptors but not all chemokines. The full names for a number of the chemokines abbreviated in the table are as follows: ELC (Ebl1 ligand chemokine); ENA-78 (epithelial-cell-derived neutrophil-activating protein); GCP-2 (granulocyte chemotactic protein 2); Gro-a, ß, y (growth-related oncogene a, ß, y); MCP-1, 2,3, or 4 (monocyte chemoattractant protein 1,2,3, or 4); Mig (monokine induced by interferon y); MIP-1a, 1 ß, or 5 (macrophage inflammatory protein 1a, 1 ß, or 5); NAP-2 (netrophil-activating protein 2); RANTES (regulated upon activation, normal T-cell expresssed and secreted); TARC (thymus- and activation-regulated chemokine.)
SOURCE: Adapted from Nelson and Krensky, 1998, Curr. Opin. Immunol. 10:265, and Baggiolini, 1998, Nature 392:565.
Adenylyl cyclase cAMP
PLCß2 IP3 DAG
TCa2+ PKC \ 1/ Actin polymerization
Adhesion Cytoskeletal Differentiation, rearrangement proliferation
Chemokines signal through receptors coupled with heterotrimeric large G proteins. Binding of a chemokine to its receptor activates many signal-transduction pathways, resulting in a variety of modifications in the physiology of the target cell. If the signal-transduction pathway is not known or incompletely worked out, dashed lines and question marks are used here to represent probable pathways. [Adapted from Premack et al, 1996, Nature Medicine 2:1174.]
Chemotaxis teins (Figure 15-8). Dramatic changes are effected by the chemokine-initiated activation of these signal transduction pathways. Within seconds, the addition of an appropriate chemokine to leukocytes causes abrupt and extensive changes in shape, the promotion of greater adhesiveness to endothe-lial walls by activation of leukocyte integrins, and the generation of microbicidal oxygen radicals in phagocytes. These signal-transduction pathways promote other changes such as the release of granular contents, proteases in neutrophils and macrophages, histamine from basophils, and cytotoxic proteins from eosinophils.
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