title: The involvement of matrix metalloproteinases in basement membrane injury in a murine model of acute allergic airway inflammation.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kumagai
authors.forename: I
authors.initials: I
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Imai
authors.forename: J
authors.initials: J
authors.lastname: Nawata
authors.forename: K
authors.initials: K
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: H
authors.initials: H
authors.lastname: Senoo
authors.forename: T
authors.initials: T
authors.lastname: Hattori
authors.forename: K
authors.initials: K
authors.lastname: Shirato
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001485:Basement Membrane / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D024061:Collagen Type III / Q000032:analysis; D024141:Collagen Type IV / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D007958:Leukocyte Count; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D023421:Models, Animal; D010047:Ovalbumin; D012130:Respiratory Hypersensitivity / Q000201:enzymology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D014132:Trachea / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D000893:Anti-Inflammatory Agents; D024061:Collagen Type III; D024141:Collagen Type IV; D019716:Tissue Inhibitor of Metalloproteinase-2; D003907:Dexamethasone; D010047:Ovalbumin; D020782:Matrix Metalloproteinases