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

doi:10.1038/ni773

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 journal › Article › peer-review

238 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 language	English (US)
Pages (from-to)	347-353
Number of pages	7
Journal	Nature immunology
Volume	3
Issue number	4
DOIs	https://doi.org/10.1038/ni773
State	Published - Apr 2002

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni773

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title = "Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency",

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.",

author = "David Corry and Kirtee Rishi and John Kanellis and Attila Kiss and Song, {Li zhen} and Jie Xu and Zena Werb and Farrah Kheradmand",

note = "Funding Information: Acknowledgments We thank A. C.White and B. Dickey for helpful comments and T. Itoh and S. Itohara for providing the MMP2–/– mice. Supported by the Caroline Weiss Law Fund for Molecular Medicine; National Institutes of Health grants K08 HL03344 and R01 HL69585 (to D. C.), K08 HL03732 and R01 HL64061 (to F. K.); and the Sandler Family Asthma Fund (to Z.W.).",

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doi = "10.1038/ni773",

language = "English (US)",

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pages = "347--353",

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AU - Corry, David

AU - Rishi, Kirtee

AU - Kanellis, John

AU - Kiss, Attila

AU - Song, Li zhen

AU - Xu, Jie

AU - Werb, Zena

AU - Kheradmand, Farrah

N1 - Funding Information: Acknowledgments We thank A. C.White and B. Dickey for helpful comments and T. Itoh and S. Itohara for providing the MMP2–/– mice. Supported by the Caroline Weiss Law Fund for Molecular Medicine; National Institutes of Health grants K08 HL03344 and R01 HL69585 (to D. C.), K08 HL03732 and R01 HL64061 (to F. K.); and the Sandler Family Asthma Fund (to Z.W.).

PY - 2002/4

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N2 - 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.

AB - 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.

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

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