HMGB1 and microparticles as mediators of the immune response to cell death.

Journal Article (Journal Article;Review)

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.

Full Text

Duke Authors

Cited Authors

  • Pisetsky, DS; Gauley, J; Ullal, AJ

Published Date

  • October 15, 2011

Published In

Volume / Issue

  • 15 / 8

Start / End Page

  • 2209 - 2219

PubMed ID

  • 21194388

Pubmed Central ID

  • PMC3166182

Electronic International Standard Serial Number (EISSN)

  • 1557-7716

Digital Object Identifier (DOI)

  • 10.1089/ars.2010.3865


  • eng

Conference Location

  • United States