Neutrophil integrins and NETosis machinery (Integrin-NET axis)

Neutrophil integrins and the NETosis machinery represent a coordinated functional unit responsible for neutrophil recruitment and the release of neutrophil extracellular traps (NETs). Integrins, particularly the beta-2 family (LFA-1 and Mac-1), mediate the firm adhesion of neutrophils to the vascular endothelium and provide the mechanical signals necessary to trigger the intracellular NETosis pathway. The machinery itself involves a cascade of enzymes including Peptidylarginine deiminase 4 (PAD4), which mediates histone citrullination, and Neutrophil Elastase (NE), which facilitates chromatin decondensation. While essential for trapping and killing pathogens, dysregulated NETosis is a major driver of tissue damage in chronic inflammatory diseases, autoimmune disorders like lupus, and pro-thrombotic states. Therapeutic strategies targeting this axis include integrin antagonists to prevent neutrophil infiltration and small molecule inhibitors of PAD4 or NE to block the formation of NETs without completely compromising systemic immunity.

Other names

Neutrophil extracellular trap machineryBeta-2 integrinsCD11/CD18 complexNETosis signaling pathwayLeukocyte integrins

Inhibition of neutrophil adhesion via beta-2 integrin blockade; inhibition of chromatin decondensation via PAD4 antagonism; inhibition of proteolytic activity via neutrophil elastase inhibitors; degradation of extracellular DNA scaffolds.