Extracellular Vesicles - Effectors of Transfusion-related Acute Lung Injury.

Abstract

Respiratory transfusion reactions represent some of the most severe adverse reactions related to receiving blood products. Of those, transfusion-related acute lung injury (TRALI) is associated with elevated morbidity and mortality. TRALI is characterized by severe lung injury associated with inflammation, pulmonary neutrophil infiltration, lung barrier leak, and increased interstitial and airspace edema which cause respiratory failure. Presently, there are few means of detecting TRALI beyond clinical definitions based on physical examination and vital signs or preventing/treating TRALI beyond supportive care with oxygen and positive pressure ventilation. Mechanistically, TRALI is thought to be mediated by the culmination of two successive pro-inflammatory hits, which typically comprise a recipient factor (1st hit - e.g. systemic inflammatory conditions) and a donor factor (2nd hit - e.g. blood products containing pathogenic antibodies or bioactive lipids). An emerging concept in TRALI research is the contribution of extracellular vesicles (EVs) in mediating the 1st and/or 2nd hit in TRALI. EVs are small, sub-cellular, membrane-bound vesicles which circulate in donor and recipient blood. Injurious EVs may be released by immune or vascular cells during inflammation, by infectious bacteria, or in blood products during storage, and can target the lung upon systemic dissemination. This review assesses emerging concepts such as how EVs: i) mediate TRALI, ii) represent targets for therapeutic intervention to prevent or treat TRALI, and iii) serve as biochemical biomarkers facilitating TRALI diagnosis and detection in at-risk patients.