High concentrations of alpha-defensins in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome.
alpha-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 alpha-defensins levels in plasma and bronchoalveolar lavage fluid (BALF) of ARDS patients to assess the kinetics of alpha-defensins in ARDS. Plasma alpha-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 alpha-defensins levels correlated with those of interleukin (IL)-8, and plasma alpha-defensins levels also correlated with Lung Injury Score. Peripheral neutrophil alpha-defensins contents were higher in ARDS than the control. IL-8 dose-dependently stimulated alpha-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 alpha-defensins from the bone marrow in ARDS, although alpha-defensins in peripheral and BALF neutrophils were mature type. In conclusion, high plasma alpha-defensins in ARDS patients result from the release of pro-defensins from bone marrow, rather than mature alpha-defensins from neutrophils that accumulate in the alveolar space. The alpha-defensins contents of peripheral neutrophils in ARDS are higher and easier to release than control.
Ashitani
Jun-Ichi
J
The Third Department of Internal Medicine, Miyazaki Medical College, Kihara 5200, Kiyotake, Miyazaki 889-1692, Japan. stajiri@fc.miyazaki-med.ac.jp
Mukae
Hiroshi
H
Arimura
Yasuji
Y
Sano
Arisa
A
Tokojima
Masatoshi
M
Nakazato
Masamitsu
M
D000368:Aged; D001853:Bone Marrow / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D007700:Kinetics; D055370:Lung Injury; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000378:metabolism*; D023084:alpha-Defensins / Q000097:blood*
D016209:Interleukin-8; D023084:alpha-Defensins; D016179:Granulocyte Colony-Stimulating Factor