The involvement of matrix metalloproteinases in basement membrane injury in a murine model of acute allergic airway inflammation

K. Kumagai, I. Ohno, K. Imai, J. Nawata, K. Hayashi, S. Okada, H. Senoo, T. Hattori, K. Shirato

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Background: Airway remodelling in asthma such as subepithelial fibrosis is thought to be the repair process that follows the continuing injury as of chronic airway inflammation. However, how acute allergic inflammation causes tissue injury in the epithelial basement membrane in asthmatic airways remains unclear. Matrix metalloproteinases (MMPs) capable of degrading almost all of the extracellular matrix components have been demonstrated to be involved in cell migration through the basement membrane in vivo and in vitro. Objective: We investigated the alterations of matrix construction and the role of MMPs in matrix degradation in the subepithelium during acute allergic airway inflammation. Methods: Airway inflammation, the ultrastructure of the subepithelium and injury of types III and IV collagen in tracheal tissues from ovalbumin (OVA)-sensitized mice after OVA inhalation with or without the administration of tissue inhibitor of metalloproteinase-2 (TIMP-2) and dexamethasone were evaluated by cell counting in bronchoalveolar lavage (BAL) fluids, electron microscopy and immunohistochemistry, respectively. Results: The disruption of the lamina densa and matrix construction and the decrease of the immunoreactivity for type IV collagen in subepithelium were observed in association with the accumulation of inflammatory cells in airways 3 days after OVA inhalation. This disorganization of the matrix components in the subepithelium, as well the cellular accumulation, was abolished by the administration of TIMP-2 and dexamethasone. The immunoreactivity for type IV collagen in the subepithelium in OVA-inhaled mice returned to the level of that in saline-inhaled mice 10 days after inhalation in association with a decrease of the cell numbers in the BAL fluid. The immunoreactivity for type III collagen was changed neither 3 nor 10 days after OVA inhalation. Conclusion: These results suggest that epithelial basement membrane gets injured by, at least in part, MMPs as a consequence of cell transmigration through the membrane during acute allergic airway inflammation.

Original languageEnglish
Pages (from-to)1527-1534
Number of pages8
JournalClinical and Experimental Allergy
Issue number10
Publication statusPublished - 2002
Externally publishedYes


  • Acute allergic airway inflammation
  • Airway remodelling
  • Corticosteroids
  • Eosinophils
  • Lamina densa
  • Lamina reticularis
  • Matrix metalloproteinases
  • Subepithelial fibrosis
  • Tissue inhibitor of metalloproteinase
  • Type IV collagen

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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