Chemokines and their receptors play a central role in the pathogenesis
of numerous, perhaps all, acute and chronic inflammatory diseases. About
50 distinct chemokines produced by a variety cell types and tissues
either c- stitutively or in response to inflammatory stimuli are
involved in a plethora of biological processes. These small secreted
proteins exert their exquisitely variegated functions upon binding to a
family of seven-transmembrane spanning G-protein coupled receptors
(GPCRs) composed of almost 20 distinct entities. The biological
activities of chemokines range from the control of leukocyte trafficking
in basal and inflammatory conditions to the regulation of hema- poiesis,
angiogenesis, tissue architecture, and organogenesis. The basis for such
diversified activities rests, on one hand, upon the ubiquitous nature of
chemokine production and chemokine receptor expression. Virtually every
cell type can produce chemokines and expresses a unique combination of
chemokine receptors. On the other hand, chemokine receptors make use of
a flexible and complex network of intracellular signaling machineries
that can regulate a variety of cellular functions ranging from cell
migration, growth, and differentiation to death. As knowledge of the
size of chemokine and chemokine receptor families rapidly reaches
completeness, much is still to be uncovered in terms of fu- tional
architecture of the chemokine system. The disparity between the large
number of chemokines and that smaller number of receptors is balanced by
the promiscuity in ligand-receptor interactions, with multiple
chemokines binding to the same receptor and several chemokines binding
to more than one receptor.
