Nature Immunology
3, 347 - 353 (2002)
Published online: 11 March 2002; | doi:10.1038/ni773
Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiencyDavid B. Corry1, 2, 3, Kirtee Rishi2, John Kanellis2, Attila Kiss2, Li-zhen Song2, Jie Xu2, Lili Feng2, Zena Werb4
& Farrah Kheradmand1, 21
Biology of Inflammation Center, Houston, TX 77030, USA. 2
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. 3
Department of Immunology, Baylor College of Medicine, Houston, TX 77030, USA. 4
Department of Anatomy, University of California, San Francisco, CA 94143-0452, USA.
Correspondence should be addressed to Farrah Kheradmand farrahk@bcm.tmc.edu or David B. Corry dcorry@bcm.tmc.eduClearance 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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