Platelet-neutrophil complex (PNC)

Platelet-neutrophil complexes (PNCs) are heterotypic cellular associations formed when activated platelets bind to neutrophils, a process central to thromboinflammation (1, 5). This interaction is primarily mediated by the binding of P-selectin (CD62P), which is translocated to the platelet surface upon activation, to P-selectin glycoprotein ligand-1 (PSGL-1) constitutively expressed on neutrophils (3, 13). Once formed, PNCs trigger a bidirectional activation loop: platelets induce neutrophils to release proinflammatory cytokines, reactive oxygen species, and neutrophil extracellular traps (NETs), while neutrophils in turn further amplify platelet activation and coagulation (6, 12). Elevated levels of circulating PNCs are recognized as sensitive biomarkers and drivers of pathology in conditions such as myocardial infarction, stroke, sepsis, and sickle cell disease (2, 9, 11). Therapeutic strategies targeting these complexes focus on disrupting the P-selectin/PSGL-1 axis or using antiplatelet agents like P2Y12 inhibitors to reduce the initial activation of platelets (5, 12, 16). While effective at reducing thrombosis and vascular inflammation, these interventions must be carefully managed to avoid significantly impairing the patient's innate immune response or increasing the risk of hemorrhage (1, 12).

Other names

Platelet-neutrophil aggregate (PNA)Platelet-leukocyte aggregate (PLA)Neutrophil-platelet interactionPlatelet satellitism

Inhibition of the physical interaction between activated platelets and neutrophils by targeting adhesion molecules, primarily blocking platelet P-selectin (CD62P) from binding to neutrophilic P-selectin glycoprotein ligand-1 (PSGL-1), or by reducing upstream platelet activation to limit the surface expression of these receptors.