| "Autoregulation" of human neutrophil activation in vitro: regulation of phorbol myristate acetate-induced neutrophil activation by cell density. | |
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MedLine Citation:
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PMID: 2159515 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phorbol myristate acetate (PMA, 10(-7) M) activation of adherent neutrophils (PMNs) led to a markedly attenuated release of superoxide anion (O2-) per cell when PMNs were activated at high density (2.85 fmol O2-/PMN at 2 million in 0.1 ml) in comparison with cells activated at low cell density (12.0 fmol O2-/PMN at 250,000 in 0.1 ml). This "autoregulatory" phenomenon was not due to a defect in the superoxide anion assay employed, to a differential adherence of neutrophils at high vs. low density, or to substrate (cytochrome c) or cell stimulus (PMA) limitation. It was associated with an inhibition of apparent NADPH oxidase activity and a leftward shift (toward a lower level of activation) in the activation profile of PMNs (as determined by FACS analysis using PMNs preloaded with 2'7'-dichlorofluorescin diacetate in which H2O2 production results in the production of the fluorescent product 2'7'-dichlorofluorescein intracellularly). Other aspects of the neutrophil activation response including arachidonic acid mobilization, phospholipid metabolism, and perhaps phosphatidylinositol turnover were also attenuated when PMNs were activated at high cell density. Studies with cells in solution, cells treated with cycloheximide, and cells treated with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid suggest that PMN contact with a surface, neutrophil protein synthesis, and an increased surface expression of the heterodimer CD11b/CD18 on PMNs all were not required for autoregulation. Finally, morphometric and morphologic examination of PMNs activated at low vs. high density revealed histologic and structural correlates associated with the attenuated PMN activation response of cells triggered at high cell density. We conclude that multiple structural and functional aspects of the PMN activation response are modulated by cell density and suggest that this property is important both in the physiologic control of neutrophil activation and in the design of in vitro assays of the neutrophil activation response. |
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Authors:
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S P Peters; F Cerasoli; K H Albertine; M H Gee; D Berd; Y Ishihara |
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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: Journal of leukocyte biology Volume: 47 ISSN: 0741-5400 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 1990 May |
Date Detail:
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Created Date: 1990-06-08 Completed Date: 1990-06-08 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 457-74 Citation Subset: IM |
Affiliation:
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Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arachidonic Acid Arachidonic Acids / metabolism Cell Count Cell Membrane / metabolism, ultrastructure Flow Cytometry Homeostasis / drug effects, physiology* Humans Hydrogen Peroxide / metabolism Inflammation / pathology Microscopy, Electron NADH, NADPH Oxidoreductases / metabolism NADPH Oxidase Neutrophils / metabolism, physiology*, ultrastructure Superoxides / metabolism Tetradecanoylphorbol Acetate / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AI24509/AI/NIAID NIH HHS; HL34014/HL/NHLBI NIH HHS; HL36237/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Arachidonic Acids; 11062-77-4/Superoxides; 16561-29-8/Tetradecanoylphorbol Acetate; 506-32-1/Arachidonic Acid; 7722-84-1/Hydrogen Peroxide; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.3.1/NADPH Oxidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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