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Published ahead of print on July 15, 2004, doi:10.1164/rccm.200404-507OC
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American Journal of Respiratory and Critical Care Medicine Vol 170. pp. 1049-1056, (2004)
© 2004 American Thoracic Society
doi: 10.1164/rccm.200404-507OC

Original Article

Presence of Activated Mobile Fibroblasts in Bronchoalveolar Lavage from Patients with Mild Asthma

Kristoffer Larsen, Ellen Tufvesson, Johan Malmström, Matthias Mörgelin, Marie Wildt, Annika Andersson, Anna Lindström, Anders Malmström, Claes-Göran Löfdahl, György Marko-Varga, Leif Bjermer and Gunilla Westergren-Thorsson

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

Correspondence and requests for reprints should be addressed to Kristoffer Larsen, BMC C13, S-221 84 Lund, Sweden. 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 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.

Key Words: asthma • bronchoalveolar lavage fluid • fibroblast • fibrosis • migration




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