PSGL-1 as a novel therapeutic target.
The first events of leukocyte recruitment into the tissues are leukocyte tethering (capture) and rolling along the vessel wall, which are mediated primarily by selectins. P-selectin glycoprotein ligand-1 (PSGL-1) is a dimeric, mucin-type glycoprotein ligand expressed by all leukocytes and is a ligand for E-, P- and L-selectin. Quantitative and qualitative differences in the expression, affinity binding to the selectins and glycosylation of PSGL-1 between leukocyte subtypes suggest that potential PSGL-1 blockade should not have broad negative consequences in physiology and host defense. PSGL-1 has a well-documented role in organ targeting during inflammation in animal models, and inhibition of PSGL-1, though challenging, represents an attractive basis for antiinflammatory strategies. The consistent number of studies accumulated in the last 10 years since PSGL-1 was first characterized should induce us to ask whether we should put more effort into developing new drugs aimed to target more effectively PSGL-1 function in human diseases.
Constantin
Gabriela
G
Division of General Pathology, Department of Pathology, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. gabriela.constantin@univr.it
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D015195:Drug Design; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000627:therapeutic use*; D008958:Models, Molecular
D000893:Anti-Inflammatory Agents; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein