High concentrations of $alpha;-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome

Abstract

α-Defensins, antimicrobial peptides localized in neutrophils, participate in tissue damage through their cytotoxic effects in neutrophil-mediated pulmonary diseases. Neutrophils play an important role in the pathogenesis of acute respiratory distress syndrome (ARDS). We measured α-defensins levels in plasma and bronchoalveolar lavage fluid (BALF) of ARDS patients to assess the kinetics of α-defensins in ARDS. Plasma α-defensins levels were higher in ARDS patients than in control subjects, and BALF levels were also higher in ARDS patients than in control subjects. In ARDS, BALF α-defensins levels correlated with those of interleukin (IL)-8, and plasma α-defensins levels also correlated with Lung Injury Score. Peripheral neutrophil α-defensins contents were higher in ARDS than the control. IL-8 dose-dependently stimulated α-defensins release from cultured neutrophils and these levels were higher in ARDS than the control. Reverse-phase high performance liquid chromatography showed high plasma levels of pro-defensins, precursors of α-defensins from the bone marrow in ARDS, although α-defensins in peripheral and BALF neutrophils were mature type. In conclusion, high plasma α-defensins in ARDS patients result from the release of pro-defensins from bone marrow, rather than mature α-defensins from neutrophils that accumulate in the alveolar space. The α-defensins contents of peripheral neutrophils in ARDS are higher and easier to release than control.