Vol.18 No.4

Review Article

The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation

Authors

Stacy P. Ardoin1 , David S. Pisetsky2

  • Departments of Internal Medicine and Pediatrics, Divisions of Rheumatology and Pediatric Rheumatology, Duke University Medical Center, DUMC Box 3212, Durham, NC, 27710, USA
  • Department of Internal Medicine, Division of Rheumatology and Medical Research Service, Durham VA Hospital, Durham, NC, USA
Received:

28 September 2007

Accepted:

6 February 2008

Published online:

17 April 2008

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Abstract

Cell death is critical to normal homeostasis, although this process, when increased aberrantly, can lead to the production of pro-inflammatory mediators promoting autoimmunity. Two novel intercellular mediators of inflammation generated during cell death are high mobility group box 1 (HMGB1) protein and microparticles (MPs). HMGB1 is a nuclear protein that functions in transcription when inside the nucleus but takes on pro-inflammatory properties when released during cell death. Microparticles are small, membrane-bound structures that extrude from cells when they die and contain cell surface proteins and nuclear material from their parent cells. MPs circulate widely throughout the vasculature and mediate long-distance communication between cells. Both MPs and HMGB1 have been implicated in the pathogenesis of a broad spectrum of inflammatory diseases, including the prototypic autoimmune conditions systemic lupus erythematosus and rheumatoid arthritis. Given their range of activity and association with active disease, both structures may prove to be targets for effective therapy in these and other disorders.

Key words

HMBG1 - Microparticles - Apoptosis - Cell death - Autoimmunity