The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway

Stefania Gardella, Cristina Andrei, Denise Ferrera, Lavinia V. Lotti, Maria R. Torrisi, Marco E. Bianchi, Anna Rubartelli

Research output: Contribution to journalArticlepeer-review

Abstract

HMGB1, a non-histone nuclear factor, acts extracellularly as a mediator of delayed endotoxin lethality, which raises the question of how a nuclear protein can reach the extracellular space. We show that activation of monocytes results in the redistribution of HMGB1 from the nucleus to cytoplasmic organelles, which display ultrastructural features of endolysosomes. HMGB1 secretion is induced by stimuli triggering lysosome exocytosis. The early mediator of inflammation interleukin (IL)-1β is also secreted by monocytes through a non-classical pathway involving exocytosis of secretory lysosomes. However, in keeping with their respective role of early and late inflammatory factors, IL-1β and HMGB1 respond at different times to different stimuli: IL-1β secretion is induced earlier by ATP, autocrinally released by monocytes soon after activation; HMGB1 secretion is triggered by lysophosphatidylcholine, generated later in the inflammation site. Thus, in monocytes, non-classical secretion can occur through vescicle compartments that are at least partially distinct.

Original languageEnglish
Pages (from-to)995-1001
Number of pages7
JournalEMBO Reports
Volume3
Issue number10
DOIs
Publication statusPublished - Oct 1 2002

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint

Dive into the research topics of 'The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway'. Together they form a unique fingerprint.

Cite this