Altered matrix production in the distal airways of individuals with asthma.
OBJECTIVE
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 (n=12) and patients with mild asthma (n=11) were cultured and incubated for 24 h with 0.4% serum, or stimulated with transforming growth factor beta1 (TGFbeta1). [(35)S]Sulfate-labelled proteoglycans in culture medium were analysed by ion exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Proliferation was measured with crystal violet, and exhaled nitric oxide was measured by the fractional nitric oxide technique.


RESULTS
Vesican production from distal fibroblasts was significantly elevated in patients with asthma compared with controls (p<0.001), and the percentage collagen-positive area in distal asthma tissue was also enhanced compared with controls (p<0.01). In addition, distal asthma fibroblasts had reduced proliferation capacity compared with those of controls (by 24%; p<0.01). Furthermore, the alveolar nitric oxide concentration was correlated to distal biglycan and perlecan production of subjects with asthma (r=-0.857, p<0.05 and r=-0.750, p<0.05 respectively)


CONCLUSIONS
It is shown that centrally and distally derived fibroblasts differ in their proteoglycan production and proliferation between central and distal tissue, and in those with asthma compared with controls. It is also demonstrated that remodelling is present in distal lung of subjects with mild asthma. This may be of importance in airway remodelling and asthma progression.
Nihlberg
Kristian
K
Experimental Medical Science, Klinikgatan 32, Lund, Sweden. kristian.nihlberg@med.lu.se
Andersson-Sjöland
Annika
A
Tufvesson
Ellen
E
Erjefält
Jonas S
JS
Bjermer
Leif
L
Westergren-Thorsson
Gunilla
G
D000328:Adult; D001249:Asthma / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001706:Biopsy; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans / Q000096:biosynthesis; D011650:Pulmonary Alveoli / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D055815:Young Adult
D011509:Proteoglycans; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D003094:Collagen