Differentiated immunoglobulins and neutrophil-related proteins in bronchoalveolar lavage fluid exosomes of acute respiratory distress syndrome

Abstract Pulmonary immune response is a critical determining factor for acute respiratory distress syndrome (ARDS). Extracellular vesicles released from lung stem and immune cells may serve as inflammatory niches involved in immune response and lung injury repair. The role of exosomal immunoglobulins (Igs) and neutrophil-related proteins in bronchoalveolar lavage (BAL) in lung immunology is unknown. We aimed to examine the content and potential role of exosomal immune proteins of ARDS patients. The abundance of exosomal proteins was quantified with a proteomic platform. Exosomal Igs and neutrophil-related proteins in BAL were analyzed with a combination of proteomic and bioinformatic software for functional enrichment, cell origin, and network analysis. There were 4,458 proteins identified and approximately 400 exosomal proteins per stage were significantly altered in patients compared with healthy controls. The number of significantly reduced exosomal Igs was dependent on the severity: 19 for mild, 38 for moderate, and 51 for severe. Of them, 32 Igs were seen in at least two stages, while 19 Igs were occurred only in severe ARDS. Most of these downregulated Igs were either heavy or light chain variable regions, indicating their diverse cell origin. In contrast, no Igs were upregulated in ARDS patients. In addition, four neutrophil-related proteins (MPO, DEFA1, CXCL8, MME) were significantly upregulated in BAL exosomes of ARDS patients. Significant differences in functional enrichment, pathway, cell origin, and network were observed among three stages of ARDS patients. Our proteomic data identified exosomal Igs and neutrophil-related proteins of ARDS that may serve as clinical biomarkers and the regulators of local immune response.