Vascular endothelial adhesion and inflammation pathways

Vascular endothelial adhesion and inflammation pathways encompass the coordinated molecular processes that regulate the recruitment and migration of leukocytes from the blood into tissues during an immune response (Ley et al., 2007, Nature Reviews Immunology). This cascade involves the activation of endothelial cells by pro-inflammatory cytokines, leading to the upregulated expression of cell adhesion molecules (CAMs) such as ICAM-1, VCAM-1, and selectins like E-selectin and P-selectin (Muller, 2013, Cardiovascular Research). These molecules interact with specific ligands and integrins on the surface of leukocytes to facilitate rolling, firm adhesion, and eventual transendothelial migration (Galkina & Ley, 2007, Arteriosclerosis, Thrombosis, and Vascular Biology). Chronic activation of these pathways is a central driver in the pathogenesis of atherosclerosis, where it promotes plaque formation, as well as in various autoimmune and chronic inflammatory disorders (Hajra et al., 2000, PNAS). Pharmacological intervention typically targets specific components of these pathways, such as integrins (e.g., Natalizumab) or selectins (e.g., Crizanlizumab), to reduce pathological inflammation (FDA, 2023). While effective, targeting these pathways can lead to significant safety concerns, including immunosuppression and increased susceptibility to opportunistic infections like progressive multifocal leukoencephalopathy (Tysabri Prescribing Information, 2023).

Other names

Endothelial-leukocyte adhesion cascadeVascular inflammatory pathwaysEndothelial activation pathwayLeukocyte recruitment cascade

Inhibition of leukocyte-endothelial interaction by blocking cell adhesion molecules (CAMs), integrins, or selectins involved in the inflammatory cascade.