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MMP-8\u2212\/\u2212 mice with ALI had greater increases in lung polymorphonuclear neutrophils (PMNs) and macrophage counts, measures of alveolar capillary barrier injury, lung elastance, and mortality than WT mice with ALI. Bronchoalveolar lavage fluid (BALF) from LPS-treated MMP-8\u2212\/\u2212 mice had more MIP-1\u03b1 than BALF from LPS-treated WT mice, but similar levels of other pro- and anti-inflammatory mediators. MIP-1\u03b1\u2212\/\u2212 mice with ALI had less acute lung inflammation and injury than WT mice with ALI, confirming that MIP-1\u03b1 promotes acute lung inflammation and injury in mice. Genetically deleting MIP-1\u03b1 in MMP-8\u2212\/\u2212 mice reduced the increased lung inflammation and injury and mortality in MMP-8\u2212\/\u2212 mice with ALI. Soluble MMP-8 cleaved and inactivated MIP-1\u03b1 in vitro, but membrane-bound MMP-8 on activated PMNs had greater MIP-1\u03b1\u2013degrading activity than soluble MMP-8. High levels of membrane-bound MMP-8 were detected on lung PMNs from LPS-treated WT mice, but soluble, active MMP-8 was not detected in BALF samples. Thus, MMP-8 has novel roles in restraining lung inflammation and in limiting alveolar capillary barrier injury during ALI in mice by inactivating MIP-1\u03b1. In addition, membrane-bound MMP-8 on activated lung PMNs is likely to be the key bioactive form of the enzyme that limits lung inflammation and alveolar capillary barrier injury during ALI.<\/jats:p>","DOI":"10.4049\/jimmunol.0900290","type":"journal-article","created":{"date-parts":[[2009,12,30]],"date-time":"2009-12-30T22:01:23Z","timestamp":1262210483000},"page":"1575-1588","source":"Crossref","is-referenced-by-count":98,"title":["Matrix Metalloproteinase-8 Inactivates Macrophage Inflammatory Protein-1\u03b1 To Reduce Acute Lung Inflammation and Injury in Mice"],"prefix":"10.1093","volume":"184","author":[{"given":"Pablo A","family":"Quintero","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin D","family":"Knolle","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa F","family":"Cala","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehong","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline A","family":"Owen","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,12,30]]},"reference":[{"key":"2026012808094021500_r1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/jlb.65.2.137","article-title":"The cell biology of leukocyte-mediated proteolysis.","volume":"65","author":"Owen","year":"1999","journal-title":"J. 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