Document Detail


HMGB1 and microparticles as mediators of the immune response to cell death.
MedLine Citation:
PMID:  21194388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In a wide variety of diseases, cell death represents both an outcome and an important step in pathogenesis. This duality occurs because cell death leads to the extracellular release of molecules and structures that can potently induce the innate immune system. These mediators include the alarmins which are endogenous cellular constituents that exit activated or dying cells to stimulate toll-like receptors (TLRs) as well as non-TLR receptors. Of alarmins, the nonhistone protein HMGB1 is the prototype. Like DNA and RNA, HMGB1 can translocate from cells as they die. The activity of HMGB1 may reflect its interaction with other molecules such as LPS, DNA, and cytokines. In addition to alarmins, dead and dying cells can release subcellular organelles called microparticles that contain cytoplasmic and nuclear constituents, including DNA and RNA. These particles can impact on many cell types to induce inflammation. The release of HMGB1 and microparticles shows important similarities, occurring with cell death as well as stimulation of certain but not all TLRs. Furthermore, nitric oxide can induce the release of both. These observations suggest that the products of dead cells can serve as important mediators to drive immune responses and promote inflammation and autoreactivity.
Authors:
David S Pisetsky; Julie Gauley; Anirudh J Ullal
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review     Date:  2011-05-05
Journal Detail:
Title:  Antioxidants & redox signaling     Volume:  15     ISSN:  1557-7716     ISO Abbreviation:  Antioxid. Redox Signal.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-02     Completed Date:  2012-03-21     Revised Date:  2013-02-11    
Medline Journal Info:
Nlm Unique ID:  100888899     Medline TA:  Antioxid Redox Signal     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2209-19     Citation Subset:  IM    
Affiliation:
Medical Research Service, Durham VA Hospital, 508 Fulton Street, Durham, NC 27705, USA. piset001@mc.duke.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Death / physiology*
DNA / metabolism
HMGB1 Protein / metabolism*
Humans
Immunity, Innate / physiology
RNA / metabolism
Toll-Like Receptors / metabolism
Grant Support
ID/Acronym/Agency:
A1082402//PHS HHS; A1083923//PHS HHS
Chemical
Reg. No./Substance:
0/HMGB1 Protein; 0/Toll-Like Receptors; 63231-63-0/RNA; 9007-49-2/DNA
Comments/Corrections

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