Stiff circulating neutrophils and enhanced thrombogenic potential in bronchiectasis increases cardiovascular risk

Résumé fourni par la source

Neutrophils mediate tissue damage in bronchiectasis through release of proteolytic enzymes and pro-inflammatory cytokines. Dysregulation of neutrophil priming/activation increases their destructive capability and modulates the cytoskeleton. Neutrophil dysregulation may also contribute to increased cardiovascular complications in patients with bronchiectasis. We evaluated neutrophil biophysical phenotype and plasma thrombogenic potential. Venous blood from 15 bronchiectasis patients and age/sex-matched healthy controls (HC), maintained at physiological oxygen tension (5% O2), was examined using Real-Time Deformability Cytometry (RT-DC). Whole blood in methylcellulose buffer was perfused through a 20mm channel at 0.03mL/s and biophysical profiles of gated neutrophils were analysed using ShapeOut software. Thrombogenic potential of platelet-poor plasma was assessed by thrombin generation assay. Bronchiectasis patient neutrophils had a higher Young’s modulus compared to HC (0.90kPa vs 0.88kPa, p=0.039), indicative of greater cell stiffness. Bronchiectasis patient plasma had a greater peak thrombin concentration (355.6nM vs 256.9nM, p=0.007) than HC, demonstrating increased thrombogenic potential. Given the association between neutrophil priming and greater cell stiffness, our results indicate that primed neutrophils may circulate in bronchiectasis patients, increasing the risk of tissue damage and extra-pulmonary sequelae. Stiff neutrophils are more likely to become trapped in narrow capillary beds. This may compound our finding of increased plasma thrombogenic potential to further increase vascular damage and cardiovascular risk in bronchiectasis.

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