Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency

David Corry, Kirtee Rishi, John Kanellis, Attila Kiss, Li zhen Song, Jie Xu, Zena Werb, Farrah Kheradmand

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

Clearance of recruited immune cells is necessary to resolve inflammatory reactions. We show here that matrix metalloproteinase 2 (MMP2), as part of an interleukin 13 (IL-13)-dependent regulatory loop, dampens inflammation by promoting the egress of inflammatory cells into the airway lumen. MMP2-/- mice showed a robust asthma phenotype and increased susceptibility to asphyxiation induced by allergens. However, whereas the lack of MMP2 reduced the influx of cells into bronchoalveolar lavage (BAL), numerous inflammatory cells accumulated in the lung parenchyma. BAL of MMP2-/- mice lacked normal chemotactic activity, whereas lung inflammatory cells from the same mice showed appropriate chemotactic responses. Thus, MMP2 establishes the chemotactic gradient required for egression of lung inflammatory cells and prevention of lethal asphyxiation.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalNature immunology
Volume3
Issue number4
DOIs
StatePublished - Apr 2002

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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