Chemokine receptor antagonists: novel therapeutics for inflammation and AIDS.
To date almost 40 human chemokines have been described, modulating a complex and overlapping set of biological activities important for basal leukocyte trafficking, as well as the extravasation and tissue infiltration of leukocytes in response to inciting agents. Chemokines appear to be key mediators in a number of inflammatory pathologies as a result of their chemotactic effects on almost every leukocyte type, including neutrophils, eosinophils, basophils, monocytes, dendritic cells, NK cells, B-cells and T-cells, together with their ability to stimulate effector functions, such as granule release and superoxide radical production from these cells. With the recent discovery that some chemokine receptors function as HIV-1 co-receptors and with accumulating evidence that chemokines may also regulate certain aspects of haematopoiesis, angiogenesis and apoptosis, the chemokines and their receptors have emerged as a new set of drug discovery targets for the pharmaceutical and biotechnology industry.
Ponath
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Department of Immunology,LeukoSite, Inc., 215 First Street, Cambridge, MA 02142, USA. paul_ponath@leukosite.com