Abstract
The diversity of integrins and their complex role in many diseases suggests great
potential for this superfamily as drug targets. The initial successes of anti-integrin
therapeutics in the treatment of thrombotic disorders suggested that similar anti-integrin
agents could be developed for the treatment of inflammatory disorders. While initially
a promising strategy, inhibition of the integrins proved to be elusive despite the
discovery of highly potent inhibitors. This is due to several reasons, including redundancy
among the integrins and the importance of integrins in key physiological systems.
Further exploration of the selective role for distinct leukocytic integrins indicated
that homing of inflammatory cells to select disease sites depends on a highly regulated
expression of discrete integrins and their ligands in limited locations. Selective
control of integrin function is also regulated by local chemokines permitting exquisite
homing of populations of inflammatory cells to disease sites. A more complete understanding
of the regulation of integrin activation in disease states will permit the development
of more effective and specific anti-integrin therapeutic agents.
Keywords
inflammation - cell adhesion molecules - therapeutic strategies
