title: Allergic airway inflammation in mice deficient for the antigen-processing protease cathepsin E.
abstract: BACKGROUND
  Allergic asthma is a Th2-type chronic inflammatory disease of the lung. It is characterized by infiltration of eosinophils, neutrophils, mast cells and T lymphocytes into the airways. Th2 cytokines like interleukin (IL)-4, IL-5 and chemokines like eotaxin are increased in the asthmatic response. The processing and presentation of exogenous antigens is important in the sensitization to an allergen. Cathepsin E (Ctse) is an intracellular aspartic endoprotease which is expressed in immune cells like dendritic cells (DCs). It was found to play an essential role in the processing and presentation of ovalbumin (OVA). The aim of the present study was to investigate the inhibition of Ctse in two different experimental models of allergic airway inflammation.
  
  
  METHODS
  Ctse wild-type (Ctse(+/+)) and Ctse-deficient (Ctse(-/-)) bone marrow-derived DCs (BMDCs) were pulsed with OVA/OVA peptide and cocultured with OVA transgenic T II (OT II) cells whose proliferation was subsequently analyzed. Two different in vivo asthma models with Ctse(+/+) and Ctse(-/-) mice were performed: an acute OVA-induced and a subchronic Phleum pratense-induced airway inflammation.
  
  
  RESULTS
  Proliferation of OT II cells was decreased when cocultured with BMDCs of Ctse(-/-) mice as compared to cells cocultured with BMDCs of Ctse(+/+) mice. In vivo, Ctse deficiency led to reduced lymphocyte influx after allergen sensitization and challenge in both investigated airway inflammation models, compared to their control groups.
  
  
  CONCLUSIONS
  Ctse deficiency leads to a reduced antigen presentation in vitro. This is followed by a distinct effect on lymphocyte influx in states of allergic airway inflammation in vivo.
authors: Department of Pneumology, Hannover Medical School, Hannover, Germany.
authors: Carolin
authors: C
authors: Pilzner
authors: Frank
authors: F
authors: Bühling
authors: Thomas
authors: T
authors: Reinheckel
authors: Caroline
authors: C
authors: Chwieralski
authors: Anchana
authors: A
authors: Rathinasamy
authors: Hans-Dieter
authors: HD
authors: Lauenstein
authors: Thomas
authors: T
authors: Wex
authors: Tobias
authors: T
authors: Welte
authors: Armin
authors: A
authors: Braun
authors: David A
authors: DA
authors: Groneberg
mesh_terms: D000208:Acute Disease; D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D020059:Cathepsin E / Q000172:deficiency* / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D031784:Phleum / Q000276:immunology; D011014:Pneumonia / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000485:Allergens; D010455:Peptides; D010047:Ovalbumin; D020059:Cathepsin E; C533926:Ctse protein, mouse