Decreased capacity of asthmatic bronchial fibroblasts to degrade collagen

The mechanisms of fibrillar collagen accumulation in asthmatic bronchi rema in unclear, an imbalance between synthesis and degradation of collagen may be implicated in this process. The aim of this study was to compare the cap acities of normal (BNF) and asthmatic (BAF) bronchial fibroblasts to degrad e collagen. Metalloproteinases and their inhibitors were measured by ELISA, types I and III procollagen synthesis was determined by liquid RIA and, fi nally, zymography was used to assess the presence of active and latent form s of MMPs. The capacity of fibroblasts to degrade collagen coated onto late x beads was evaluated by flow cytometry. Our results showed that MMP-2 secr etion was significantly higher in BNF when compared to BAF and this was con firmed by gelatin zymography, In BNF culture, TIMP-1 and MMP-1 secretions p ositively correlated with types I and III procollagen synthesis. However, i n BAF, this correlation was negative. This suggests that a balance exists b etween collagen synthesis and degradation in BNF and that this balance is c ompromised in BAF, On the other hand, BAF did show significantly reduced ca pacity to degrade collagen when compared to that of BNF, This reduced phago cytic activity was not associated with a decrease in collagen receptor expr ession. This study establishes for the first time that a relationship exist s between metalloproteinases enzyme dysregulation and the reduced capacity of asthmatic bronchial fibroblast to degrade collagen. These events may she d light on why accumulation of collagen can be observed in asthmatic airway s. (C) 2001 Elsevier Science B.V./International Society of Matrix Biology. All rights reserved.