CD14-positive extracellular vesicles in bronchoalveolar lavage fluid as a new biomarker of acute respiratory distress syndrome

Abstract

Recent studies have indicated that extracellular vesicles (EV) may play a role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS). EV have been identified as potential biomarkers of disease severity and prognosis in other pulmonary diseases. We sought to characterize the EV phenotype within ARDS patient broncho-alveolar lavage fluid (BAL), and to determine whether BAL EV could be utilized as a potential biomarker in ARDS. BAL was collected from sepsis patients with and without ARDS, and from esophagectomy patients post-operatively (of whom a subset later developed ARDS during hospital admission). BAL EV were characterized with regards to size, number and cell of origin. Sepsis patients with ARDS had significantly higher numbers of CD14+/CD81+ monocyte-derived BAL EV than sepsis patients without ARDS (p=0.015). However, the converse was observed in esophagectomy patients who later developed ARDS (p=0.003). Esophagectomy patients who developed ARDS also had elevated CD31+/CD63+ and CD31+/CD81+ endothelial-derived BAL EV (p≤0.02) compared to esophagectomy patients who did not develop ARDS. Further studies are required to determine whether CD31+ BAL EV may be a predictive biomarker for ARDS in esophagectomy patients. CD14+/CD81+ BAL EV numbers were significantly higher in those patients with sepsis-related ARDS who died during the 30 days following ICU admission (p=0.027). Thus, CD14+/CD81+ BAL EV are a potential biomarker for disease severity and mortality in sepsis-related ARDS. These findings provide the impetus to further elucidate the contribution of these EV to ARDS pathogenesis.

Exosomal MicroRNAs: An Emerging Important Regulator in Acute Lung Injury

“…Recent studies have found that EVs with CD14 + in BALF can also serve as a new biomarker for ARDS. Elevated counts of EVs with CD14 + /CD81 + in BALF of patients with sepsis-associated ARDS are associated with the increased mortality of patients with ARDS . SCAP usually leads to high mortality in ARDS.…”

Dual Role of Extracellular Vesicles in Sepsis-Associated Kidney and Lung Injury

“…In fact, EVs were more abundant in BALF of ARDS patients compared with patients with hydrostatic oedema and had greater pro-coagulant activity, mediated by a higher expression of TF [ 107 ]. Compared with septic patients without lung involvement, patients with sepsis-related ARDS had higher number of CD14+/CD81+ monocyte-derived EVs in BALF and this signature was associated with dismal outcome [ 108 ].…”

“…These data were expanded in a study showing that patients who underwent esophagectomy and further developed ARDS had higher concentration of endothelial-derived CD31 + EVs in BALF compared with healthy subjects. Considered together, these studies suggest that the secretome of monocytes and ECs play a role in ARDS pathogenesis and in identifying those patients who are at risk of developing the syndrome [ 108 ]. Table 3 showed a synthesis of clinical trials assessing the safety and efficacy of intravenous treatment with MSCs and MSC-derived EVs in human subjects with ARDS.…”

The Roles of Extracellular Vesicles in Sepsis and Systemic Inflammatory Response Syndrome

“…Extracellular vesicles from monocytes were found in the bronchoalveolar lavage (BAL) of septic patients and were shown to be significantly associated with ARDS and the mortality of patients ( 61 ). A significant release of Exos was observed in an experimental in vitro setting of LPS-treated alveolar macrophages, which induces lung inflammation and was significantly ameliorated via Exo downregulation due to hydrochloride hydrate treatment ( 62 ).…”