| A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. | |
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MedLine Citation:
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PMID: 20813919 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B(4) (LTB(4)). LTA(4)H also possesses aminopeptidase activity with unknown substrate and physiological importance; we identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflammation, PGP was degraded by LTA(4)H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA(4)H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA(4)H to prevent LTB(4) generation may not reduce neutrophil recruitment because of elevated levels of PGP. |
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Authors:
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Robert J Snelgrove; Patricia L Jackson; Matthew T Hardison; Brett D Noerager; Andrew Kinloch; Amit Gaggar; Suresh Shastry; Steven M Rowe; Yun M Shim; Tracy Hussell; J Edwin Blalock |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-09-02 |
Journal Detail:
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Title: Science (New York, N.Y.) Volume: 330 ISSN: 1095-9203 ISO Abbreviation: Science Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-08 Completed Date: 2010-10-20 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0404511 Medline TA: Science Country: United States |
Other Details:
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Languages: eng Pagination: 90-4 Citation Subset: IM |
Affiliation:
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Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham Lung Health Center, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rjs198@imperial.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylation Animals Bronchoalveolar Lavage Fluid / chemistry Cells, Cultured Chemokines, CXC / metabolism Chemotaxis, Leukocyte Epoxide Hydrolases / antagonists & inhibitors, isolation & purification, metabolism* Female Humans Inflammation Leukotriene B4 / metabolism Lung / immunology*, metabolism, pathology Mice Mice, Inbred BALB C Mice, Inbred C57BL Neutrophils / enzymology, immunology, physiology* Oligopeptides / metabolism* Orthomyxoviridae Infections / immunology, metabolism, pathology Pneumococcal Infections / immunology, metabolism, pathology Pneumonia / immunology*, metabolism, pathology, therapy Proline / analogs & derivatives*, metabolism Pulmonary Disease, Chronic Obstructive / immunology, metabolism, pathology Smoke* Tobacco |
| Grant Support | |
ID/Acronym/Agency:
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082727/Z/07/Z//Wellcome Trust; 1K23DK075788/DK/NIDDK NIH HHS; 1R03DK084110-01/DK/NIDDK NIH HHS; HL07783/HL/NHLBI NIH HHS; HL087824/HL/NHLBI NIH HHS; HL090999/HL/NHLBI NIH HHS; HL102371-A1/HL/NHLBI NIH HHS; K08HL091127/HL/NHLBI NIH HHS; P171/03/C1/048//Medical Research Council; P30 DK079337/DK/NIDDK NIH HHS; P30AR050948/AR/NIAMS NIH HHS; P30CA13148/CA/NCI NIH HHS; P50 AT00477/AT/NCCAM NIH HHS; R01 HL077783-05/HL/NHLBI NIH HHS; R01 HL077783-06/HL/NHLBI NIH HHS; R01 HL087824-02/HL/NHLBI NIH HHS; R01 HL090999-02S1/HL/NHLBI NIH HHS; R01 HL090999-04/HL/NHLBI NIH HHS; R01 HL102371-02/HL/NHLBI NIH HHS; RR19231/RR/NCRR NIH HHS; U54CA100949/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokines, CXC; 0/Oligopeptides; 0/Smoke; 0/prolyl-glycyl-proline; 147-85-3/Proline; 71160-24-2/Leukotriene B4; EC 3.3.2.-/Epoxide Hydrolases; EC 3.3.2.-/leukotriene A4 hydrolase |
| Comments/Corrections | |
Comment In:
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Science. 2010 Oct 1;330(6000):40-1
[PMID:
20929796
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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