PWE-143 Abnormal Platelets and the Formation of Activated Neutrophil-platelet Complexes Following Platelet Administration Induces Neutrophil Activation and Release of Reactive Oxygen Species in Liver Cirrhosis

    loading  Checking for direct PDF access through Ovid

Abstract

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.

Related Topics

    loading  Loading Related Articles