Rationale Morphological changes in the small airways due to excess subepithelial matrix deposition may contribute to obstructive physiology in asthma. The pathobiology of this process is poorly understood, but may result from the discoordinate regulation of matrix active cytokines, structural proteins, and protease: anti-protease activities. To examine this process, we followed the global expression of relevant extracellular matrix components during initiation and resolution of allergic inflammation in a well-characterized aspergillus asthma model (Haczku, et al, Am J Respir Cell Mol Biol. 2001,25:45-50) Methods Multiple gene expression was determined by real-time PCR in whole lung lysates at baseline, and 1, 7 and 10 days post nasal allergen challenge in sensitized mice. Matrix metalloprotease (MMP) activity was detected in BAL fluid by zymography; selected proteases and their tissue inhibitors (TIMPs) were also analyzed by ELISA. Results Analysis of gene expression revealed early (day 1) induction of collagen type 2a1, with late (day 7-10) induction of collagen 1, 3a1, 4a3 and 6a1 and laminins. Several MMPs and their corresponding TIMPs appeared coordinately at peak inflammation (by gene and BAL protein levels), while Adamts family protease expression was exclusively a late phenomenon. Gelatinolytic activity at this time was predominantly accounted for by MMP9. Conclusion Specific structural matrix proteins are induced consecutively as a result of allergen challenge, as are certain proteases involved in their processing. The delayed kinetics of some of them suggests that they are part of the repair process by which subepithelial deposition might ultimately occur.
Full conference title:
2008 American Academy of Allergy, Asthma, and Immunology Annual Meeting
- AAAAI 2008 (64th)