Altered matrix production in the distal airways of individuals with asthma

Abstract

Background and aims Although increasing evidence suggests involvement of the distal airway in all stages of asthma, it is not known whether structural changes (defined as airway remodelling) occur in the distal airways of subjects with mild asthma and those with atopy. The aim of this study was to compare control subjects and those with mild asthma in relation to fibroblast phenotypes and remodelling in central and distal airways. Methods Distal and central fibroblasts from controls (n¼12) and patients with mild asthma (n¼11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor b1 (TGFb1).[ 35 S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfateepolyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique.

iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma

“…In our previous study with more patients, the synthesis of proteoglycans perlecan, biglycan and decorin from distal lung fibroblasts all correlated negatively to alveolar NO in asthmatic subjects but no correlations were detected in healthy subjects. Interestingly, there was no correlation between alveolar NO and proteoglycan production in healthy controls (2). There may be possibility of other biochemical pathways potentially modulated by iNOS.…”

“…In mild asthma we recently demonstrated the presence of remodelling in distal airways as shown by increased collagen content in the tissue. In addition a negative correlation was found between alveolar NO and the production of the proteoglycans biglycan and decorin by fibroblasts from patients with mild asthma (2). We therefore hypothesized that there is an ongoing remodelling that is linked to iNOS in the distal airways of patients with mild asthma.…”

“…Primary human distal lung fibroblast cultures were established from the distal biopsies from patients with mild asthma (n=6) and healthy control subjects (n=5) as previously described (2). Some control lung fibroblasts (n=3) were instead isolated from lung explants from unused donors meant for lung transplantation (21).…”

“…Primary fibroblasts were cultured in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10% foetal Clone III serum (FCIII, Hyclone, Logan, UT, US), 1% L-glutamine, 0.5% gentamicin and 5 g/ml amphotericin B (all from Gibco BRL, Paisley, UK). The fibroblast cultures were stained with specific antibodies to verify the mesenchymal identity and to estimate the purity, as previously described (2,21 …”

“…It is now becoming evident that also the distal airways are subjected to inflammatory and structural changes (2,3). In addition to the chronic inflammation associated with asthma, there are multiple structural alterations in the lung tissue, a phenomenon collectively termed airway remodelling.…”