Document Detail

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.
MedLine Citation:
PMID:  21215311     Owner:  NLM     Status:  MEDLINE    
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.
Saurabh Chatterjee; Olivier Lardinois; Suchandra Bhattacharjee; Jeff Tucker; Jean Corbett; Leesa Deterding; Marilyn Ehrenshaft; Marcelo G Bonini; Ronald P Mason
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2011-01-04
Journal Detail:
Title:  Free radical biology & medicine     Volume:  50     ISSN:  1873-4596     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-08     Completed Date:  2011-06-17     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  988-99     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Inc.
National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
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MeSH Terms
Blotting, Western
Caspase 3 / metabolism
Cell Death*
DNA / biosynthesis*
Dendritic Cells / metabolism*
Enzyme-Linked Immunosorbent Assay
Lipopolysaccharides / pharmacology
Mice, Inbred C57BL
Microscopy, Confocal
Oxidative Stress*
Protein Biosynthesis*
Sepsis / metabolism*,  pathology
Grant Support
Z01 ES050139-13/ES/NIEHS NIH HHS; Z01 ES050139-13/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Lipopolysaccharides; 9007-49-2/DNA; EC 3.4.22.-/Caspase 3

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