Cell adhesion molecules (Integrins and Selectins) (CAMs)

Integrins and selectins are two distinct families of cell surface receptors that cooperatively mediate the recruitment of leukocytes from the blood into tissues, a process central to the inflammatory response [1]. Selectins, including E-selectin, P-selectin, and L-selectin, initiate the "rolling" phase of leukocyte recruitment by binding to carbohydrate ligands such as P-selectin glycoprotein ligand-1 (PSGL-1) on the vascular endothelium [3]. This transient interaction slows the leukocyte, allowing it to sense local chemokines that trigger the activation of integrins, such as Lymphocyte Function-associated Antigen-1 (LFA-1) and Very Late Antigen-4 (VLA-4) [1][2]. Once activated, these integrins bind firmly to endothelial ligands like Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1), facilitating firm adhesion and subsequent transendothelial migration [1][4]. In chronic inflammatory and autoimmune diseases, the overexpression of these molecules leads to excessive leukocyte infiltration and tissue damage [2]. Therapeutic agents like natalizumab (targeting alpha-4 integrin) and crizanlizumab (targeting P-selectin) disrupt these interactions to treat conditions like multiple sclerosis and sickle cell disease [4][5]. However, because these pathways are also essential for normal immune surveillance, their inhibition can lead to side effects such as increased susceptibility to opportunistic infections like progressive multifocal leukoencephalopathy (PML) [4]. References: [1] Ley K, et al. Nat Rev Immunol. 2007;7(9):678-89. [2] Desgrosellier JS, Cheresh DA. Nat Rev Cancer. 2010;10(1):9-22. [3] McEver RP. Curr Opin Cell Biol. 2015;33:31-7. [4] Mitroulis I, et al. Trends Pharmacol Sci. 2015;36(6):393-401. [5] Ataga KI, et al. N Engl J Med. 2017;376(5):429-39.

Other names

Adhesion receptorsEndothelial-leukocyte adhesion moleculesLeukocyte adhesion moleculesIntegrins and selectins

Inhibition of leukocyte-endothelial interaction by blocking the binding of integrins or selectins to their respective ligands (e.g., ICAM-1, VCAM-1, MAdCAM-1, or PSGL-1), thereby preventing leukocyte rolling, firm adhesion, and transmigration into inflamed tissues.