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.
authors.affiliation: Biology of Inflammation Center, Houston, TX 77030, USA. dcorry@bcm.tmc.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Corry
authors.forename: Kirtee
authors.initials: K
authors.lastname: Rishi
authors.forename: John
authors.initials: J
authors.lastname: Kanellis
authors.forename: Attila
authors.initials: A
authors.lastname: Kiss
authors.forename: Li-zhen
authors.initials: LZ
authors.lastname: Song Lz
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Lili
authors.initials: L
authors.lastname: Feng
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Farrah
authors.initials: F
authors.lastname: Kheradmand
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D054413:Chemokine CCL11; D054414:Chemokine CCL17; D054410:Chemokine CCL7; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004151:Dipeptides / Q000494:pharmacology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D005260:Female; D018793:Interleukin-13 / Q000008:administration & dosage / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000494:pharmacology; D010047:Ovalbumin / Q000009:adverse effects; D011014:Pneumonia / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D011480:Protease Inhibitors / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C515457:Ccl11 protein, mouse; C499538:Ccl17 protein, mouse; C515451:Ccl7 protein, mouse; D054413:Chemokine CCL11; D054414:Chemokine CCL17; D054410:Chemokine CCL7; D019742:Chemokines, CC; D016207:Cytokines; D004151:Dipeptides; D018793:Interleukin-13; D061965:Matrix Metalloproteinase Inhibitors; D018945:Monocyte Chemoattractant Proteins; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; D011480:Protease Inhibitors; D010047:Ovalbumin; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2