ELEVATED CONCENTRATIONS OF DEFENSINS IN BRONCHOALVEOLAR LAVAGE FLUID IN DIFFUSE PANBRONCHIOLITIS

Human neutrophils contain three isoforms of antimicrobial and cytotoxi c peptides in the azurophil granules, which belong to a family of mamm alian neutrophil peptides named defensins, sere we investigate the rol e of these peptides in diffuse panbronchiolitis (DPB). Defensins (huma n neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay i n bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 pati ents with idiopathic pulmonary fibrosis (IPF) and If healthy adults, T he concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects, DPB and IPF patients a lso had significantly higher plasma concentrations of defensins than c ontrols,In patients with DPB, BALF concentration of defensins correlat ed significantly with neutrophil count or BALF concentration of interl eukin (IL)-L. Immnunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar ep ithelial cells. fn vitro studies showed an enhanced extracellular rele ase of defensins following stimulation of neutrophils with phorbol myr istate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human reco mbinant IL-8, Treatment of DPB with macrolides for 6 months significan tly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defen sins in the airway in diffuse panbronchiolitis, and suggest that defen sins may be a marker of neutrophil activity in this disease.