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Published ahead of print on July 15, 2004, doi:10.1164/rccm.200404-507OC

Am. J. Respir. Crit. Care Med., Volume 170, Number 10, November 2004, 1049-1056

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Submitted on April 19, 2004
Accepted on July 14, 2004

Presence of Activated Mobile Fibroblasts in Bronchial Alveolar Lavage from Mild Asthmatic Patients

Kristoffer Larsen1*, Ellen Tufvesson2, Johan Malmstrom1, Matthias Morgelin1, Marie Wildt1, Annika Andersson1, Anna Lindstrom1, Anders Malmstrom1, Claes-Goran Lofdahl2, Gyorgy Marko-Varga3, Leif Bjermer2, and Gunilla Westergren-Thorsson1

1 Department of Cell and Molecular Biology, Lund University, Lund, Sweden, 2 Department of Respiratory Medicine and Allergology, University Hospital Lund, Lund, Sweden, 3 Department of Analytical Chemistry, Lund University, Lund, Sweden

* To whom correspondence should be addressed. E-mail: kristoffer.larsen{at}medkem.lu.se.

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 non-asthmatic control subjects (n=17). The elongated fibroblasts migrated twice as far when compared to 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 mild asthmatic patients, results that may play a role in formation of airway fibrosis.
Key words: Asthma, fibrosis, bronchoalveolar lavage fluid, migration, fibroblast




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