Introduction The susceptibility to developing infection is well recognised in cirrhosis and circulating neutrophil dysfunction including excessive production of reactive oxygen species (ROS) is a major contributor to innate immune paresis. Platelets also play a key role modulating inflammation by interacting with neutrophils, secreting inflammatory mediators and influencing phagocytosis/apoptosis. The aim of this study was to examine platelet-neutrophil interactions in relation to ROS production and following healthy platelet exposure in patients with liver cirrhosis.
Methods Neutrophil-platelet interactions were characterised in 7 patients (6M; mean age 54) (Child-Pugh 11–14) in a paired crossover study with 7 healthy controls (HC). Neutrophils and platelets were isolated separately and incubated alone and together ex-vivo in zero, 50:1 and 100:1 platelet:neutrophil ratios. Neutrophils were stained with anti-CD16-PE and anti-CD11b-APC-Cy7 (macrophage-1 antigen) using flow cytometry. Platelets were stained with anti-CD41a-APC (glycoprotein IIb/IIIa) and complexes were identified as staining for CD11b/CD16/CD41a. Neutrophils were stimulated with phorbol myristate acetate which induces ROS production quantified by conversion of dihydrorhodamine-123 to rhodamine-123.
Results The addition of platelets to neutrophils (100:1) significantly reduced ROS production (p < 0.01). HC platelets were significantly better at reducing ROS production than cirrhotic platelets (p < 0.05). Neutrophil-platelet complex formation was significantly higher when HC platelets were added to unstimulated neutrophils than cirrhotic platelets (Graph 1) with a 3.3 fold increase in neutrophil endothelial adhesion capability
Conclusion Cirrhotic platelets have a reduced capability to reduce neutrophil priming and ROS production. However, paradoxically administration of healthy platelets increases neutrophil-platelet complex formation and neutrophil adhesion capabilities which may promote endothelial activation and susceptibility to infection.
Disclosure of Interest None Declared.
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