title: Presence of activated mobile fibroblasts in bronchoalveolar lavage from patients with mild asthma.
abstract: Activated fibroblasts are suggested to be involved in the deposition of extracellular matrix in the formation of peribronchial fibrosis in asthma. We report the novel finding of activated elongated fibroblasts accompanied by elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12 patients with mild asthma (= 42%), whereas no fibroblasts were observed in the control subjects without asthma (n = 17). The elongated fibroblasts migrated twice as far when compared with fibroblasts from corresponding bronchial biopsies from the same patients, accompanied by an induced expression of RhoA and Rac1, indicating that the increased expression of these proteins are linked to increased migratory capabilities. Moreover, the elongated fibroblasts had an elevated production of the proteoglycans biglycan, versican, perlecan, and decorin, which correlated to an active cytoplasm in these cells. Differential expression patterns between the two fibroblast groups in motility-regulating proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock protein 20, were identified by two-dimensional electrophoresis and mass spectrometry. These findings indicate the presence of activated and mobile fibroblasts accompanied by an induced inflammatory response outside the airway epithelium in patients with mild asthma, results that may play a role in formation of airway fibrosis.
authors.affiliation: Department of Cell and Molecular Biology, Lund University, Lund, Sweden. kristoffer.larsen@medkem.lu.se
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Larsen
authors.forename: Ellen
authors.initials: E
authors.lastname: Tufvesson
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Marie
authors.initials: M
authors.lastname: Wildt
authors.forename: Annika
authors.initials: A
authors.lastname: Andersson
authors.forename: Anna
authors.initials: A
authors.lastname: Lindström
authors.forename: Anders
authors.initials: A
authors.lastname: Malmström
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Löfdahl
authors.forename: György
authors.initials: G
authors.lastname: Marko-Varga
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000473:pathology* / Q000503:physiopathology; D001707:Biopsy, Needle; D015153:Blotting, Western; D016535:Bronchial Hyperreactivity / Q000175:diagnosis*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D002465:Cell Movement; D002478:Cells, Cultured; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000473:pathology* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index