Document Detail


Role of macrophages in the generation of circulating blood nucleosomes from dead and dying cells.
MedLine Citation:
PMID:  12775567     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
After apoptosis or necrosis, macrophages clear dead cells by phagocytosis. Although this process is efficient, circulating nucleosomes can occur in certain diseases, presumably reflecting either increased production or impaired clearance. To investigate the generation of blood nucleosomes, graded numbers of apoptotic and necrotic cells were administered to healthy mice, and levels of blood nucleosomes and DNA were determined. Using Jurkat cells as a model, nucleosomes and DNA were detected in the blood after the administration of 108 apoptotic or necrotic cells per mouse by the intraperitoneal route. The kinetics of the response were similar for both types of cells. The role of macrophages was assessed by eliminating these cells with clodronate liposomes or silica. Although clodronate treatment alone produced a peak level of blood DNA, the subsequent administration of dead cells caused no change in DNA levels. In contrast, silica treatment alone did not elicit a blood DNA response, though this treatment limited the rise in DNA from administered cells. Molecular studies showed that the blood DNA following the administration of apoptotic or necrotic cells arose from the mouse and the Jurkat cells, and its size distribution was consistent with apoptosis. Together, these findings suggest that the generation of blood nucleosomes depends on macrophages, with apoptosis a concomitant of a high burden of dead and dying cells.
Authors:
Ning Jiang; Charles F Reich; David S Pisetsky
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-05-29
Journal Detail:
Title:  Blood     Volume:  102     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-08     Completed Date:  2003-10-17     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2243-50     Citation Subset:  AIM; IM    
Affiliation:
Division of Rheumatology, Duke University Medical Center, Durham, NC 27705, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites / pharmacology
Cell Death / physiology*
Clodronic Acid / pharmacology
DNA / blood
Female
Humans
Jurkat Cells
Macrophages, Peritoneal / drug effects,  physiology*
Mice
Mice, Inbred BALB C
Necrosis
Nucleosomes / metabolism*
Phagocytosis / physiology
Grant Support
ID/Acronym/Agency:
AI 44808/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antimetabolites; 0/Nucleosomes; 10596-23-3/Clodronic Acid; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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