Decreased allergic lung inflammatory cell egression and increased susceptibility to asphyxiation in MMP2-deficiency.
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.
Corry
David B
DB
Biology of Inflammation Center, Houston, TX 77030, USA. dcorry@bcm.tmc.edu
Rishi
Kirtee
K
Kanellis
John
J
Kiss
Attila
A
Song Lz
Li-zhen
LZ
Xu
Jie
J
Feng
Lili
L
Werb
Zena
Z
Kheradmand
Farrah
F
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
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