Autophagy regulation in heme-induced neutrophil activation is associated with microRNA expression on transfusion-related acute lung injury

Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of death after transfusion therapy. The pathogenesis of TRALI is associated with neutrophil activation in the lungs, causing endothelial damage and capillary leakage, and thus neutrophil extravasation. Heme-related molecules derived from the hemolysis of red blood cell components have been recognized as a stimulator, inducing neutrophil activation at TRALI. To investigate post-transcriptional changes of the neutrophil at TRALI, we performed heme-related molecules induced reactive oxygen species production in the neutrophil as a model. Neutrophils were isolated from heparinized peripheral blood and stimulated with heme-related molecules. After stimulation, reactive oxygen species production, degranulation, phagocytosis activity, and miRNA expression profile of neutrophil were analyzed by luminol assay, flow cytometry, and real-time polymerase chain reaction. The expression of miRNA targeting NADPH oxidase and autophagy in the neutrophil activation of TRALI was explored. The expression profile of miRNAs will be a useful predictor of disease severity and for the grading of patients for transfusion.