Authors: Rossi, Barbara; Constantin, Gabriela

Source: Inflammation & Allergy - Drug Targets (Formerly Current Drug Targets - Inflammation & Allergy), Volume 7, Number 2, June 2008 , pp. 85-93(9)

Publisher: Bentham Science Publishers

Abstract:

Leukocyte migration into the tissues represents a key process in the pathogenesis of inflammatory diseases. Data obtained in clinical trials have convincingly shown that inhibition of leukocyte migration into the target organs represents an effective therapeutic approach for diseases in which inflammation has a noxious effect. Leukocyte tethering and rolling are the earliest steps of leukocyte adhesion cascade in inflamed vessels. Selectins are type I transmembrane glycoproteins that bind sialylated carbohydrate structures in a calcium-dependent manner and are involved in the tethering and rolling of leukocytes under physiological and pathological conditions. Three selectins have been identified: L-, P- and Eselectin. Current understanding of the glycosylation-dependent selectin function reveals a complex role for selectins and their ligands during inflammatory diseases. Among selectin ligands, mucin P-selectin glycoprotein ligand-1 (PSGL-1) binds all three selectins and has a well-documented role in organ targeting during inflammation in animal models. However, although inhibition of selectins and their ligands in animal models of inflammatory diseases has proven the validity of this approach in vivo, only a limited number of anti-selectin drugs have been tested in humans. Recent results obtained in clinical trials for asthma and psoriasis show that, although very challenging, the development of selectin antagonists holds concrete promise for the therapy of inflammatory diseases.

Keywords: Selectins; mucins; rolling; leukocyte trafficking; inflammation

Document Type: Research article

DOI: http://dx.doi.org/10.2174/187152808785107633

Publication date: 2008-06-01

More about this publication?

• Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

Related content

• In this: publication
• By this: publisher
• In this Subject: Allergy & Immunology ,  Pharmacology
• By this author: Rossi, Barbara ;  Constantin, Gabriela

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers