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. 2021 Nov 26;10(12):3323. doi: 10.3390/cells10123323

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© 2021 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 (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Selected examples of mechanisms for HMGB1 release. (A) HMGB1 lacks a secretory signal sequence and is instead packed into secretory lysosomes in hematopoietic cells, before being released extracellularly. (B) Pyroptosis and necrosis are both lytic processes that generate HMGB1 release, (C) Inflammasome-activated gasdermin D creates pore formation in the outer cell membrane enabling HMGB1 release even before cell lysis may occur. (D) Stimulated nociceptors release HMGB1 in a retrograde manner.