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. 2015 Jun 16;5(2):219–253. doi: 10.3390/diagnostics5020219

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

PMC Copyright notice

Overview: functions of HMGB1 and sRAGE. HMGB1 is released as single molecule during necrosis while it is set free as complex bound to nucleosomes in apoptosis/secondary necrosis. In the extracellular space, HMGB1 binds to various receptors like TLR-2, TLR-4 and RAGE on the surface of macrophages, dendritic cells (DC) and other antigen presenting cells (APC), leading to inhibited fusion of phagosomes and lysosomes within these cells. This, in turn, promotes presentation of phagocyted antigens with effective specific T-cell response. sRAGE derived from alternative splicing or proteolytic cleavage can act as a decoy receptor for HMGB1. As circulating biomarkers, high levels of HMGB1 and low levels of sRAGE correlate with poor prognosis (adapted from [103] with permission from De Gruyter).