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Presence of Activated Mobile Fibroblasts in Bronchial Alveolar Lavage from Mild Asthmatic Patients
Author(s) -
Larsen K,
Nilsson K,
Tufvesson E,
Malmström J,
Wildt M,
Andersson A,
Malmström A,
Löfdahl CG,
MarkoVarga G,
Bjermer L,
WestergrenThorsson G
Publication year - 2005
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130117ab.x
Subject(s) - myofibroblast , bronchoalveolar lavage , biglycan , extracellular matrix , pathology , fibroblast , fibrosis , chemistry , lung , microbiology and biotechnology , medicine , biology , decorin , proteoglycan , in vitro , biochemistry
The remodeling process in the lung of asthmatic patients results in a deposition of connective tissue and extracellular matrix components (ECM), which has been described as a subepithelial fibrosis. Fibroblasts, with the phenotypic appearance of myofibroblasts, are considered as the key source of the ECM in the fibrotic tissue. Furthermore, has the ECM molecule biglycan shown to correlate to the hyperactivity of the lung of asthmatic patients. In this study, we report the novel finding of a stretched fibroblast phenotype from bronchoalveolar lavage fluid (BALF) in 30% of the asthmatic subjects (n = 13). No fibroblasts were obtained in BALF from any of the nonasthmatic control subjects (n = 17). These BALF fibroblasts with several characteristics of a myofibroblast displayed increased migratory capacity, accompanied by an induced expression of the small GTPases RhoA and Rac1, when compared to myofibroblasts from corresponding lung biopsies. Data also shows that patients with BALF myofibroblast also have more cells in their lung tissue near to the basement membrane that stain for markers for mesechymal progenitor cells. Moreover, the BALF‐myofibroblasts showed an increase in production of several types of proteoglycans like biglycan. By adding biglycan to normal fibrobalsts it is further possible to mimic the migratory type of myofibroblast found in BALF. To study differences in protein expression pattern between the two phenotypes, we used a gel‐based proteomic technique in combination with MALDI‐TOF mass spectrometry. BALF‐myofibroblast displayed an increase in heat shock protein 20 (HSP20) and myofibroblasts from biopsies displayed an increase in chloride intracellular channel protein (CLIC) and cofilin. These proteins are all known to regulate cell migration by interacting with the actin cytoskeleton. In summery, data demonstrates that biglycan and mesenchymal progenitor cells might have an important role in the early ‐remodeling process in asthmatic patients and are potential future biomarkers for sub‐epithelial fibrosis formation.