Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines

The mechanisms that initiate allergic lung inflammation are relevant to expression of diseases such as asthma, but the factors underlying resolution of inflammation are equally important. Previously, we demonstrated the importance of matrix metalloproteinase 2 (MMP2) for airway egression of lung eosinophils, a critical anti-inflammatory mechanism without which mice are rendered highly susceptible to lethal asphyxiation. Here we show that leukocyte MMP9 is the dominant airway MMP controlling inflammatory cell egression. The allergic lung phenotype of MMP9(-/-) mice was similar to WT and was not altered by concomitant deletion of the MMP2 gene ( double knockout; dko). However, inflammatory cells accumulated aberrantly in the lungs of allergen-challenged MMP9(-/-) and dko mice and fewer eosinophils and neutrophils were present in bronchoalveolar lavage. These aberrant cellular trafficking patterns were explained by disruption of transepithelial chemokine gradients, in MMP2(-/-) mice affecting only eotaxin (CCL11), but in MMP9(-/-) and dko mice involving eotaxin, MARC (CCL7), and TARC (CCL17). Thus, by establishing multiple transepithelial chemokine gradients, MMP9 is broadly implicated in the resolution of allergic inflammation, an essential protective mechanism that overlaps with a more limited role played by MMP2.
Publisher
FEDERATION AMER SOC EXP BIOL
Issue Date
2004-04
Language
ENG
Keywords

BRONCHIAL EPITHELIAL-CELLS; MATRIX METALLOPROTEINASES; AIRWAY HYPERREACTIVITY; ADAPTIVE IMMUNITY; GELATINASE B; MURINE MODEL; IN-VIVO; ASTHMA; MICE; EOSINOPHILS

Citation

FASEB JOURNAL, v.18, no.6, pp.995 - 995

ISSN
0892-6638
DOI
10.1096/fj.03-1412fje
URI
http://hdl.handle.net/10203/5826
Appears in Collection
MSE-Journal Papers(저널논문)
  • Hit : 309
  • Download : 2
  • Cited 0 times in thomson ci
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡClick to seewebofscience_button
⊙ Cited 119 items in WoSClick to see citing articles inrecords_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0