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The nuclear protein HMGB1 is secreted by monocytes via a non‐classical, vesicle‐mediated secretory pathway
Author(s) -
Gardella Stefania,
Andrei Cristina,
Ferrera Denise,
Lotti Lavinia V,
Torrisi Maria R,
Bianchi Marco E,
Rubartelli Anna
Publication year - 2002
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1093/embo-reports/kvf198
Subject(s) - secretory protein , microbiology and biotechnology , secretory pathway , secretion , hmgb1 , nuclear protein , chemistry , biology , biochemistry , golgi apparatus , gene , immunology , inflammation , endoplasmic reticulum , transcription factor
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.