Integrin Receptors
VLA-4 (very late antigen 4,3 α4β1-integrin, CD49d/CD29) plays a major role in the regulation of immune cell recruitment to inflamed endothelia and sites of inflammation. It is expressed on the cellular surface of mononuclear leucocytes: eosinophils, basophils, lymphocytes and monocytes, and mediates cell-cell adhesion to vascular cell adhesion molecule-1 (VCAM1) on the endothelium[1]. VLA-4 thus participates in antigen presenting cell-lymphocyte interactions, retention and mobilization of immature progenitors in the bone marrow, cancer cell trafficking, metastasis, and other events[2]. In recent years, VLA-4 antagonists have shown great promise in treating inflammatory disorders in a number of animal models[3].
[1] Z. Diamant et al. Effect of a very late antigen-4 receptor antagonist on allergen-induced airway responses and inflammation in asthma. Clin. Exp. Allergy. 2005, 35, 1080-1087.
[2] A. Chigaev et al. Discovery of very late antigen-4 (VLA-4, alpha4beta1 integrin) allosteric antagonists. J. Biol. Chem. 2011, 286, 5455-5463.
[3] K.C. Lin et al. Very late antigen 4 (VLA4) antagonists as anti-inflammatory agents. Curr. Opin. Chem. Biol 1998, 2, 453-457.