MCP-4 AND LEUKOCYTE TRAFFICKING AND ACTIVATION

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Chemokines are a family of secreted proteins that play a critical regulatory role in directing different types of while blood cells to sites of infection of tissue damage. Regulation of the host immune response by such molecules is important for combating bacterial and viral infection, and for the destruction of transformed cells that could otherwise lead to tumors. However, the improper regulation or expression of these molecules can lead to a dysregulated immune response that can contribute to a variety of inflammatory conditions, including allergic and autoimmune diseases. Consequently, understanding the roles of immuno- regulatory molecules such as chemokines is important for the development of new immunotherapies to inhibit an inappropriate inflammatory response. This knowledge would also be relevant to the design of new vaccines that would augment the host immune response to tumor growth. The aim of this proposal is to further characterize the biological activities of a newly discovered chemokine, MCP-4. Expression of related chemokines is induced by bacterial lipopolysaccarides, which are an active component of Coley's toxins. Some chemokines have been shown to be effective for promoting tumor regression in animal models; others have been associated with asthma, psoriasis and atherosclerosis. Therefore, understanding the properties of MCP-4 is essential for evaluating its therapeutic potential.