Increased concentrations of human beta-defensins in plasma and bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis

Abstract

Background: Human β-defensin (HBD)-1 and -2 are antimicrobial peptides present in the respiratory tract. Recent reports have indicated reduced activity of β-defensins in cystic fibrosis, suggesting that β-defensins may play an important role in the pathological process of chronic respiratory tract infection. Diffuse panbronchiolitis (DPB) is a progressive disease characterised by frequent episodes of superimposed infection, typically caused by Pseudomonas aeruginosa. The aim of this study was to elucidate the role of these antimicrobial peptides in this disease. Methods: The concentrations of HBD-1 and HBD-2 in plasma and bronchoalveolar lavage (BAL) fluid from 33 patients with DPB and 30 normal adults were measured by radioimmunoassay. Localisation of HBD-2 was investigated immunohistochemically in an open lung biopsy specimen obtained from a patient with DPB. Results: High concentrations of HBD-1 and HBD-2 were noted in BAL fluid from DPB patients. Increased plasma concentrations of HBD-2, but not HBD-1, were found in patients with DPB compared with control subjects. In patients with DPB the HBD-2 concentration in BAL fluid correlated significantly with the numbers of cells recovered from the BAL fluid (total cells, neutrophils, and lymphocytes) and with the BAL fluid concentration of IL-1β. Synthetic HBD-2, but not HBD-1, had dose dependent bactericidal activity against P aeruginosa. Treatment of 14 patients with macrolides significantly reduced BAL fluid concentrations of HBD-2 but not HBD-1 or plasma concentrations of HBD-1 and HBD-2. Immunohistochemistry of lung tissue showed localisation of HBD-2 in the epithelia of the distal bronchioles. Conclusions: These results indicate that β-defensins, particularly HBD-2, participate in antimicrobial defence in the respiratory tract in DPB, and that the BAL fluid concentration of HBD-2 may be a useful marker of airway inflammation in patients with DPB.

Differential Regulation of β-Defensin Expression in Human Skin by Microbial Stimuli

“…It is interesting to note that we found a fairly consistent 3-to 4-fold increase in the hBD-1 expression. In bronchoalveolar lavage fluid from patients with inflammatory lung disease (diffuse panbronchiolitis), the hBD-1 levels were found to be ϳ4-fold higher than in healthy volunteers (15). This increase in hBD-1 production is of the same order of magnitude as the increase of the hBD-1 expression in the skin.…”

“…Although inflamed skin and other epithelia greatly increase the production of hBD-3 (9, 13), it is not known how the expression of hBD-3 is regulated. The expression of hBD-1 has been deemed constitutive (14), but there is evidence that it too may be somewhat increased by inflammation (15,16). When we analyzed biopsy specimens of highly inflamed squamous epithelia by immunohistochemistry we found separate areas with intense staining for each hBD-1, hBD-2, and hBD-3.…”

Identification of hBD-3 in respiratory tract and serum: the increase in pneumonia

“…The concentrations of both HNP-1 and hBD-2 increased in the serum and BAL fluid during the acute phase of respiratory infections, returning to basal levels after the completion of therapy [25][26][27]. Serum HNP-1 and hBD-2 concentrations also increased in noninfectious pulmonary diseases, including idiopathic pulmonary fibrosis [27] and diffuse panbronchiolitis [24,29]. The serum concentrations of hBD-3 also increased in the acute phase of bacterial pneumonia, normalising in the recovery phase.…”

“…In contrast, hBD-2 is expressed by type-2 alveolar epithelial cells [24]. This differential distribution of these two defensins may contribute to their unique functions in innate host defences to invading microbes within the respiratory system.…”

“…The current authors previously determined the concentrations of three additional defensins (HNP-1, hBD-1 and hBD-2) in the serum and bronchoalveolar lavage (BAL) fluid during pulmonary disease states [9,[24][25][26][27][28][29]. The concentrations of both HNP-1 and hBD-2 increased in the serum and BAL fluid during the acute phase of respiratory infections, returning to basal levels after the completion of therapy [25][26][27].…”