| Characterization of human neutrophil and endothelial cell ligand-operated extracellular acidification rate by microphysiometry: impact of reoxygenation. | |
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MedLine Citation:
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PMID: 9536019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Neutrophil (PMN) activation and recruitment are coordinated by ligand-operated surface receptors. These responses are involved in the tissue injury that follows hypoxia/reoxygenation. Here, we report that inflammatory mediators each evoke distinct and characteristic extracellular acidification rates (EAR) in both PMN and endothelial cells (EC) as measured by a Cytosensor microphysiometer. Leukotriene B4 (LTB4) and the peptide N-formylmethionyl-leucyl-phenylalanine were the most potent activators of EAR, whereas other potent stimuli including interleukin-8 and platelet-activating factor only weakly stimulated EAR in PMN. In contrast, other lipid-derived PMN mediators such as prostaglandin E2 and lipoxin A4 (LXA4) did not evoke EAR. Ligand-operated EAR exhibited desensitization as well as ligand specificity and sensitivity to pertussis toxin. Human endothelial cell agonists including histamine, prostacyclin stable analog and LXA4 each gave sharply different EAR responses, with only histamine evoking an EAR in these cells. Hypoxia/reoxygenation did not alter ligand-operated EAR from PMN, and similarly LTB4-stimulated PMN transendothelial migration, a functional response, was not influenced by either PMN or EC exposure to intervals of hypoxia/reoxygenation. LXA4 stable analogs inhibited PMN transendothelial migration (1 nM-1 microM), and this PMN-EC responsiveness to inhibition by a lipoxin stable analog (e.g., 16-phenoxy-LXA4) was enhanced approximately 2 log orders of magnitude after hypoxia/reoxygenation. Results demonstrate that ligand-receptor interactions evoke characteristic profiles of EAR and that some well-characterized ligand-receptor pairs (including interleukin-8, platelet-activating factor, prostaglandin E2 or LXA4) on these cell types either weakly activate the EAR pathway or are silent. Furthermore, hypoxia/reoxygenation did not alter LTB4 PMN responses but did heighten responsiveness to 16-phenoxy-LXA4, which suggests a potential protective role in leukocyte-mediated injury. |
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Authors:
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K Gronert; S P Colgan; C N Serhan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of pharmacology and experimental therapeutics Volume: 285 ISSN: 0022-3565 ISO Abbreviation: J. Pharmacol. Exp. Ther. Publication Date: 1998 Apr |
Date Detail:
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Created Date: 1998-05-12 Completed Date: 1998-05-12 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376362 Medline TA: J Pharmacol Exp Ther Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 252-61 Citation Subset: IM |
Affiliation:
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Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesia, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Inflammatory Agents, Non-Steroidal
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pharmacology Cell Hypoxia Dinoprostone / pharmacology Eicosanoids / pharmacology Endothelium, Vascular / drug effects*, metabolism Humans Hydroxyeicosatetraenoic Acids / pharmacology Inflammation Mediators / pharmacology* Leukotriene B4 / pharmacology Ligands Lipoxins* N-Formylmethionine Leucyl-Phenylalanine / pharmacology Neutrophils / drug effects*, metabolism Pertussis Toxin Sodium-Hydrogen Antiporter / drug effects, metabolism Virulence Factors, Bordetella / toxicity |
| Grant Support | |
ID/Acronym/Agency:
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DK50189/DK/NIDDK NIH HHS; GM38765/GM/NIGMS NIH HHS; P01-DK50305/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Inflammatory Agents, Non-Steroidal; 0/Eicosanoids; 0/Hydroxyeicosatetraenoic Acids; 0/Inflammation Mediators; 0/Ligands; 0/Lipoxins; 0/Sodium-Hydrogen Antiporter; 0/Virulence Factors, Bordetella; 0/lipoxin A4; 363-24-6/Dinoprostone; 59880-97-6/N-Formylmethionine Leucyl-Phenylalanine; 71160-24-2/Leukotriene B4; EC 2.4.2.31/Pertussis Toxin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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