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

Life Sci. 2004 Jul 16;75(9):1123-34. doi: 10.1016/j.lfs.2004.01.028.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Bone Marrow / metabolism
  • Bronchoalveolar Lavage Fluid / chemistry*
  • Chromatography, High Pressure Liquid
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-8 / blood
  • Kinetics
  • Lung Injury
  • Male
  • Middle Aged
  • Neutrophils / metabolism
  • Respiratory Distress Syndrome, Adult / blood
  • Respiratory Distress Syndrome, Adult / metabolism*
  • alpha-Defensins / blood*

Substances

  • Interleukin-8
  • alpha-Defensins
  • Granulocyte Colony-Stimulating Factor