| Modulation of neutrophil apoptosis by murine pulmonary microvascular endothelial cell inducible nitric oxide synthase. | |
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MedLine Citation:
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PMID: 20833133 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutrophils contribute significantly to ALI (acute lung injury) through adhesion to pulmonary microvascular endothelial cells (PMEC), trans-PMEC migration and alveolar infiltration. Trans-PMEC migration delays expression of neutrophil apoptosis, which promotes intra-alveolar neutrophil survival and neutrophil mediated ALI. We assessed the role of neutrophil vs PMEC inducible nitric oxide (NO) synthase (iNOS) in modulating neutrophil apoptosis. Apoptosis of wild-type vs iNOS-/- neutrophils was quantified by microscopy and FACS annexin-V binding. In a murine model of ALI, neutrophils isolated by BAL(broncho-alveolar lavage) from iNOS-/- mice had increased expression of apoptosis after 24h culture ex vivo than wild-type neutrophils (15.2±3.3 vs 3.0±0.4%, mean±sd, p<0.01). Apoptosis rates of isolated bone marrow iNOS+/+ vs iNOS-/- neutrophils were similar under basal and LPS/IFN-γ stimulation, and following LPS/IFN-γ-stimulated trans-PMEC migration. Apoptosis of both iNOS+/+ and iNOS-/- neutrophils was inhibited by trans-PMEC migration only across iNOS+/+ PMEC (1.6±0.3 and 1.5±0.3%, respectively; p<0.05 for each vs non-migrated neutrophils) but not across iNOS-/- PMEC (4.3±1 and 3.1±0.6%, respectively). PMEC iNOS-dependent inhibition of neutrophil apoptosis was independent of changes in neutrophil caspase-3 activity. We conclude that PMEC iNOS, but not neutrophil iNOS, has an important inhibitory effect on neutrophil apoptosis during trans-PMEC neutrophil migration, which is independent of caspase-3 activity. Further studies will define the mechanism of PMEC iNOS-dependent inhibition of neutrophil apoptosis and assess the potential relevance of this phenomenon in human neutrophils and ALI. |
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Authors:
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Lefeng Wang; Sanjay Mehta; Chris Gillis; Cedrin Law; Ravi Taneja |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-15 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 401 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-18 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 207-12 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Centre for Critical Illness Research, Lawson Health Research Institute, London Health Sciences Center, London, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis* Bronchoalveolar Lavage Caspase 3 / metabolism Cell Movement Endothelium, Vascular / enzymology* Lung / blood supply* Mice Mice, Mutant Strains Microvessels / cytology, enzymology Neutrophils / enzymology, physiology* Nitric Oxide Synthase Type II / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse; EC 3.4.22.-/Caspase 3 |
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