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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
Inflammatory lung injury is probably regulated by the balance between proteases and protease inhibitors together with oxidants and antioxidants, and proinflammatory and anti-inflammatory cytokines. Rat tissue inhibitor of metalloprotease-2 (TIMP-2) and secreted leukoprotease inhibitor (SLPI) were cloned, expressed, and shown to be up-regulated at the levels of mRNA and protein during lung inflammation in rats induced by deposition of IgG immune complexes. Using immunoaffinity techniques, endogenous TIMP-2 in the inflamed lung was shown to exist as a complex with 72- and 92-kDa metalloproteinases (MMP-2 and MMP-9). In inflamed lung both TIMP-2 and SLPI appeared to exist as enzyme inhibitor complexes. Lung expression of both TIMP-2 and SLPI appeared to involve endothelial and epithelial cells as well as macrophages. To assess how these endogenous inhibitors might affect the lung inflammatory response, animals were treated with polyclonal rabbit Abs to rat TIMP-2 or SLPI. This intervention resulted in significant intensification of lung injury (as revealed by extravascular leak of albumin) and substantially increased neutrophil accumulation, as determined by cell content in bronchoalveolar lavage (BAL) fluids. These events were correlated with increased levels of C5a-related chemotactic activity in BAL fluids, while BAL levels of TNF-alpha and chemokines were not affected by treatment with anti-TIMP-2 or anti-SLPI. The data suggest that endogenous TIMP-2 and SLPI dynamically regulate the intensity of lung inflammatory injury, doing so at least in part by affecting the generation of the inflammatory mediator, C5a.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigen-Antibody Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C5a,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteinase Inhibitory Proteins...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Secretory Leukocyte Peptidase...,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Slpi protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0022-1767
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pubmed:author |
pubmed-author:BleavinsM RMR,
pubmed-author:BlessN MNM,
pubmed-author:CrouchL DLD,
pubmed-author:GibbsD FDF,
pubmed-author:GipsonT STS,
pubmed-author:JohnsonK JKJ,
pubmed-author:McConnellP CPC,
pubmed-author:MuellerW TWT,
pubmed-author:SarmaVV,
pubmed-author:ShanleyT PTP,
pubmed-author:TeferaWW,
pubmed-author:WardP APA,
pubmed-author:YounkinE MEM
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
162
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3653-62
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10092827-Acute Disease,
pubmed-meshheading:10092827-Alveolitis, Extrinsic Allergic,
pubmed-meshheading:10092827-Amino Acid Sequence,
pubmed-meshheading:10092827-Animals,
pubmed-meshheading:10092827-Antigen-Antibody Complex,
pubmed-meshheading:10092827-Base Sequence,
pubmed-meshheading:10092827-Bronchoalveolar Lavage Fluid,
pubmed-meshheading:10092827-Chemokines,
pubmed-meshheading:10092827-Chemotaxis, Leukocyte,
pubmed-meshheading:10092827-Cloning, Molecular,
pubmed-meshheading:10092827-Complement C5a,
pubmed-meshheading:10092827-Immune Sera,
pubmed-meshheading:10092827-Immunoglobulin G,
pubmed-meshheading:10092827-Lung,
pubmed-meshheading:10092827-Male,
pubmed-meshheading:10092827-Metalloendopeptidases,
pubmed-meshheading:10092827-Molecular Sequence Data,
pubmed-meshheading:10092827-Protein Biosynthesis,
pubmed-meshheading:10092827-Proteinase Inhibitory Proteins, Secretory,
pubmed-meshheading:10092827-Proteins,
pubmed-meshheading:10092827-RNA, Messenger,
pubmed-meshheading:10092827-Rats,
pubmed-meshheading:10092827-Rats, Long-Evans,
pubmed-meshheading:10092827-Secretory Leukocyte Peptidase Inhibitor,
pubmed-meshheading:10092827-Serine Proteinase Inhibitors,
pubmed-meshheading:10092827-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:10092827-Tumor Necrosis Factor-alpha
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pubmed:year |
1999
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pubmed:articleTitle |
Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury.
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pubmed:affiliation |
Department of Pathology, University of Michigan, Ann Arbor 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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