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Mice Lacking 12/15-Lipoxygenase have Attenuated Airway Allergic Inflammation and Remodeling.

Författare

Summary, in English

Arachidonate 15-lipoxygenase (LO)-1 has been implicated in allergic inflammation and asthma. The overall effect of 15-LO in allergic inflammation in vivo is, however, unclear. This study investigates systemic allergen sensitization and local allergic airway inflammation and remodeling in mice lacking the murine 12/15-LO, the ortholog to human 15-LO-1. Upon systemic sensitization with intraperitoneal ovalbumin, 12/15 LO(-/-) mice produced elevated levels of allergen-specific IgE compared to wild type (Wt) controls. However, when challenged with repeated aerosolized allergen sensitized 12/15 LO(-/-) mice had an impaired development of airway allergic inflammation compared to Wt controls, as indicated by reduced BAL fluid leukocytes (eosinophils, lymphocytes macrophages) and Th2 cytokines (IL-4, IL-5, IL-13) as well as tissue eosinophils. Allergen-induced airway epithelial proliferation was also significantly attenuated in 12/15 LO(-/-) mice whereas goblet cell hyperplasia was unaffected. However, 12/15 LO(-/-) mice had significantly reduced luminal mucus secretions compared to Wt controls. The repeated allergen challenges resulted in a dramatic increase of alpha-smooth muscle-actin positive alveolar cells in the peripheral airways, a phenomenon that was significantly less developed in 12/15 LO(-/-) mice. In conclusion, our data suggest that 12/15 LO(-/-) mice, although having a fully developed systemic sensitization, did not establish a fully developed allergic airway inflammation and associated manifestations of central and peripheral airway remodeling. These data suggest that 12/15-LO derived metabolites play an important pathophysiological role in allergen-induced inflammation and remodeling. Hence, pharmacologic targeting of the human 15-LO-1 may represent an attractive therapeutic strategy to control inflammation and remodeling in asthma.

Publiceringsår

2008-12

Språk

Engelska

Sidor

648-656

Publikation/Tidskrift/Serie

American Journal of Respiratory Cell and Molecular Biology

Volym

39

Issue

6

Dokumenttyp

Artikel i tidskrift

Förlag

American Thoracic Society

Ämne

  • Cell and Molecular Biology

Nyckelord

  • Allergens
  • Animals
  • Antibodies
  • Antibody Specificity
  • Apoptosis
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Caspase 3
  • Cell Count
  • Cytokines
  • Eosinophilia
  • Goblet Cells
  • Hyperplasia
  • Hypersensitivity
  • Immunization
  • Inflammation
  • Leukocytes
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Ovalbumin
  • Journal Article
  • Research Support, Non-U.S. Gov't

Status

Published

Forskningsgrupp

  • Airway Inflammation and Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1535-4989