Neutrophil adhesion machinery

The neutrophil adhesion machinery is a coordinated system of cell surface receptors and ligands that facilitates the recruitment of neutrophils from the bloodstream to sites of infection or tissue injury (Ley K, et al., Nat Rev Immunol, 2007). This process, known as the leukocyte adhesion cascade, involves sequential steps: rolling mediated by selectins (L-, E-, and P-selectin), activation by chemokines, and firm adhesion mediated by integrins such as Lymphocyte Function-associated Antigen-1 (LFA-1) and Macrophage-1 antigen (Mac-1) binding to Intercellular Adhesion Molecule-1 (ICAM-1) (Alon R, et al., Immunity, 2021). Dysregulation of this machinery is a hallmark of chronic inflammatory diseases, including rheumatoid arthritis and inflammatory bowel disease, and genetic defects in these components lead to Leukocyte Adhesion Deficiency (LAD) (StatPearls, 2023). Pharmacological agents targeting this machinery, such as integrin antagonists (e.g., natalizumab) or selectin inhibitors (e.g., crizanlizumab), are used to treat various inflammatory and hematologic conditions by preventing excessive neutrophil infiltration (FDA, 2023). However, therapeutic modulation of these pathways carries significant safety concerns, most notably an increased risk of serious infections due to impaired immune surveillance (Kapur R, et al., Blood, 2013).

Other names

Leukocyte adhesion cascadeNeutrophil recruitment machineryLeukocyte-endothelial adhesion systemNeutrophil extravasation machinery

Inhibition of leukocyte-endothelial interaction through the blockade of selectin-mediated rolling or integrin-mediated firm adhesion.