Neutrophil gelatinase-associated lipocalin as a potential novel biomarker for ventilator-associated lung injury

Xiao, Rui; Chen, Rongchang

VALI has recently been of primary concern for clinicians and researchers. The reduction in mortality associated with low tidal volume ventilation in patients with acute lung injury, and acute respiratory distress syndrome has resulted in an increased research interest toward the underlying mechanism of VALI (16) . The roles of the innate immune response and inflammation in the pathogenesis of VALI have been extensively studied in recent years. It has previously been suggested High-PIP, high peak inflation pressure; Low-PIP, low peak inflation pressure; PEEP, positive end-expiratory pressure; HV, high-volume; LV, low-volume. that inflammation may not be integral to the initiation of VALI; however, prevalent data in the field suggests a major pathogenetic role of inflammation and lung neutrophil recruitment. Therefore, investigators have searched for biological markers of VALI and therapeutic targets that may facilitate treatment. NGAL of the lipocalin superfamily, was originally isolated from specific neutrophil granules (6, 7) . NGAL protein levels are typically very low in various biological fluids (17) . Previous studies have demonstrated that NGAL expression is associated with acute injury, particularly acute kidney injury. However, an association between NGAL and acute lung injury has not yet been reported. The present study characterized the expression profile of NGAL in mice subjected to different mechanical ventilation protocols. NGAL mRNA and protein expression levels in lung tissue increased under all mechanical ventilation treatments; however, a significant increase was observed following high-volume or high-PIP mechanical ventilation. A similar NGAL increase was further detected in BAL fluid and serum, and was notably increased following high-volume or high-PIP mechanical ventilation. NGAL expression was time-dependent under high-volume mechanical ventilation treatment. Immunohistochemical localization studies revealed increased NGAL expression in lung endothelium, alveolar epithelial cells, and infiltrating neutrophils. NGAL is easily detected in serum and BAL fluid (10, 11) . The results of the present study verify the role of NGAL as a novel and potential biomarker for VALI. A previous study revealed that plasma concentrations of NGAL were increased in oleic acid-induced acute lung injury and a conventional mechanical ventilation model in piglets (18) . Serum NGAL levels were additionally significantly increased in lung transplant patients (19) .