Leukocyte-endothelial adhesion interface

The leukocyte-endothelial adhesion interface is a complex, multi-step molecular environment where circulating leukocytes interact with the vascular endothelium to exit the bloodstream and enter tissues (Ley et al., Nat Rev Immunol, 2007). This interface is not a single protein but a functional site involving several families of adhesion molecules, including selectins, integrins, and members of the immunoglobulin superfamily like ICAM-1 and VCAM-1 (Springer, Nature, 1994). The process begins with selectin-mediated rolling, followed by chemokine-induced activation of integrins, which then bind firmly to endothelial ligands to allow for crawling and transendothelial migration (Vestweber, Nat Rev Immunol, 2015). In pathological states such as chronic inflammation, autoimmune disorders, and atherosclerosis, this interface is overactive, leading to excessive tissue damage (Muller, Trends Immunol, 2011). Therapeutic targeting of this interface has been successful through the development of monoclonal antibodies like Natalizumab and Vedolizumab, which block specific integrins to treat multiple sclerosis and inflammatory bowel disease, respectively (Danese, Gut, 2015). However, because these interactions are vital for normal immune surveillance, systemic blockade can lead to significant safety concerns, such as an increased risk of opportunistic infections like progressive multifocal leukoencephalopathy (Bloomgren et al., N Engl J Med, 2012).

Other names

Leukocyte-endothelial interactionLeukocyte recruitment cascadeLeukocyte extravasation interfaceEndothelial-leukocyte adhesion

Competitive inhibition of adhesion molecule binding (e.g., blocking integrin-ligand or selectin-ligand interactions) to prevent leukocyte attachment and extravasation.