Chemokines are a family of 8-10 kD cytokines with 20-50% similarity in their amino acid sequences that chemoattract leukocytes of every type. We were first to observe that IL 8, IP-10, MIP-1alpha-beta, and MCP-1,2,3 all chemoattract T cells. In addition, IL 8 induces neutrophils to degranulate and thus to release defensins 1 and 2 as well as azurocidin/CAP 37 which are each also potent T cell chemoattractants. Injections of the above chemokines into chimeric SCID mice reconstituted with human T cells causes human T cells to infiltrate the injection site together with the appropriate murine leukocytes: neutrophils in the case of IL 8, monocytes in response to all the others. We also established that MCP-1 and RATES chemoattract mast cells, Serum Amyloid A is chemotactic for neutrophils and monocytes and vasointestinal peptide is a potent chemoattractant of T lymphocytes as well as monocytes. The expression of receptors for various chemokines is up and down-regulated by other cytokines and bacterial products. The CMV genome has been found to encode several C-C chemokine receptor homologues and they are expressed on infected cell which can then migrate in response to chemokines such as MIP-1alpha. We have produced mutated IL 8 receptors with truncated caraboxyl intracytoplasmic tails that lose their binding, chemotactic and signalling capacity. Overall, these observations imply that chemokines play an important role in host defenses.
