| Oxidative stress induces protein and DNA radical formation in follicular dendritic cells of the germinal center and modulates its cell death patterns in late sepsis. | |
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MedLine Citation:
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PMID: 21215311 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Profound depletion of follicular dendritic cells (FDCs) is a hallmark of sepsis-like syndrome, but the exact causes of the ensuing cell death are unknown. The cell death-driven depletion contributes to immunoparalysis and is responsible for most of the morbidity and mortality in sepsis. Here we have utilized immuno-spin trapping, a method for detection of free radical formation, to detect oxidative stress-induced protein and DNA radical adducts in FDCs isolated from the spleens of septic mice and from human tonsil-derived HK cells, a subtype of germinal center FDCs, to study their role in FDC depletion. At 24h post-lipopolysaccharide administration, protein radical formation and oxidation were significantly elevated in vivo and in HK cells as shown by ELISA and confocal microscopy. The xanthine oxidase inhibitor allopurinol and the iron chelator desferrioxamine significantly decreased the formation of protein radicals, suggesting the role of xanthine oxidase and Fenton-like chemistry in radical formation. Protein and DNA radical formation correlated mostly with apoptotic features at 24h and necrotic morphology of all the cell types studied at 48h with concomitant inhibition of caspase-3. The cytotoxicity of FDCs resulted in decreased CD45R/CD138-positive plasma cell numbers, indicating a possible defect in B cell differentiation. In one such mechanism, radical formation initiated by xanthine oxidase formed protein and DNA radicals, which may lead to cell death of germinal center FDCs. |
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Authors:
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Saurabh Chatterjee; Olivier Lardinois; Suchandra Bhattacharjee; Jeff Tucker; Jean Corbett; Leesa Deterding; Marilyn Ehrenshaft; Marcelo G Bonini; Ronald P Mason |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural Date: 2011-01-04 |
Journal Detail:
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Title: Free radical biology & medicine Volume: 50 ISSN: 1873-4596 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-08 Completed Date: 2011-06-17 Revised Date: 2012-09-19 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: United States |
Other Details:
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Languages: eng Pagination: 988-99 Citation Subset: IM |
Copyright Information:
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Published by Elsevier Inc. |
Affiliation:
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National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA. chatterjees2@niehs.nih.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western Caspase 3 / metabolism Cell Death* DNA / biosynthesis* Dendritic Cells / metabolism* Enzyme-Linked Immunosorbent Assay Lipopolysaccharides / pharmacology Male Mice Mice, Inbred C57BL Microscopy, Confocal Oxidative Stress* Protein Biosynthesis* Sepsis / metabolism*, pathology |
| Grant Support | |
ID/Acronym/Agency:
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Z01 ES050139-13/ES/NIEHS NIH HHS; Z01 ES050139-13/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipopolysaccharides; 9007-49-2/DNA; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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