Targeting selectins for the treatment of inflammatory diseases.
BACKGROUND
Selectins mediate tethering and rolling of leukocytes to the vascular endothelium, the first adhesive step in the recruitment of immune cells to inflamed tissues. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic, brain, lung, heart and skin inflammation, atherosclerosis and cancer progression. Because blockade of the steps of leukocyte recruitment has been predicted to interrupt leukocyte extravasation, pharmacological interference with the function of key molecules in the multistep recruitment cascade represents a promising strategy for therapeutic intervention in inflammatory disorders. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in preclinical and clinical studies associated with inflammation.


METHODS
This article explores the experimental studies describing the beneficial effects of selectin modulators in the treatment of inflammatory diseases.


CONCLUSIONS
Many of the selectin-directed compounds have not held up to the high expectations, in some cases due to overlapping and mutually compensating functions of selectins or suboptimal pharmacokinetic properties of the compounds, while other agents appear to be more promising candidates and have already entered clinical trials.
University of Messina, Department of Biological and Environmental Sciences , Viale Ferdinando Stagno D'Alcontres, Messina 31-98166 , Italy.
Daniela
D
Impellizzeri
Salvatore
S
Cuzzocrea
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D019087:Selectins / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D019087:Selectins