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

Nat Immunol. 2002 Apr;3(4):347-53. doi: 10.1038/ni773. Epub 2002 Mar 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Asthma / chemically induced
  • Asthma / immunology*
  • Asthma / mortality
  • Asthma / physiopathology
  • Chemokine CCL11
  • Chemokine CCL17
  • Chemokine CCL7
  • Chemokines, CC / pharmacology
  • Chemotaxis / immunology
  • Cytokines / genetics
  • Dipeptides / pharmacology
  • Disease Models, Animal
  • Disease Susceptibility / immunology
  • Female
  • Interleukin-13 / administration & dosage
  • Interleukin-13 / immunology
  • Lung / immunology
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / immunology*
  • Matrix Metalloproteinase Inhibitors
  • Metalloendopeptidases / antagonists & inhibitors
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocyte Chemoattractant Proteins / pharmacology
  • Ovalbumin / adverse effects
  • Pneumonia / immunology*
  • Pneumonia / mortality
  • Pneumonia / physiopathology
  • Protease Inhibitors / pharmacology
  • Up-Regulation

Substances

  • Ccl11 protein, mouse
  • Ccl17 protein, mouse
  • Ccl7 protein, mouse
  • Chemokine CCL11
  • Chemokine CCL17
  • Chemokine CCL7
  • Chemokines, CC
  • Cytokines
  • Dipeptides
  • Interleukin-13
  • Matrix Metalloproteinase Inhibitors
  • Monocyte Chemoattractant Proteins
  • N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide
  • Protease Inhibitors
  • Ovalbumin
  • Metalloendopeptidases
  • Matrix Metalloproteinase 2