EMAIL THIS PAGE TO A FRIEND

Cell death and differentiation

Macrophage endocytosis of high-mobility group box 1 triggers pyroptosis.


PMID 24769733

Abstract

Macrophages can be activated and regulated by high-mobility group box 1 (HMGB1), a highly conserved nuclear protein. Inflammatory functions of HMGB1 are mediated by binding to cell surface receptors, including the receptor for advanced glycation end products (RAGE), Toll-like receptor (TLR)2, TLR4, and TLR9. Pyroptosis is a caspase-1-dependent programmed cell death, which features rapid plasma membrane rupture, DNA fragmentation, and release of proinflammatory intracellular contents. Pyroptosis can be triggered by various stimuli, however, the mechanism underlying pyroptosis remains unclear. In this study, we identify a novel pathway of HMGB1-induced macrophage pyroptosis. We demonstrate that HMGB1, acting through RAGE and dynamin-dependent signaling, initiates HMGB1endocytosis, which in turn induces cell pyroptosis. The endocytosis of HMGB1 triggers a cascade of molecular events, including cathepsin B release from ruptured lysosomes followed by pyroptosome formation and caspase-1 activation. We further confirm that HMGB1-induced macrophage pyroptosis also occurs in vivo during endotoxemia, suggesting a pathophysiological significance for this form of pyroptosis in the development of inflammation. These findings shed light on the regulatory role of ligand-receptor internalization in directing cell fate, which may have an important role in the progress of inflammation following infection and injury.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

PRS2287
Anti-ASC antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
AV40231
Anti-EXOSC3 (AB1) antibody produced in rabbit, affinity isolated antibody
AV40230
Anti-EXOSC3 (AB2) antibody produced in rabbit, affinity isolated antibody, lyophilized powder
SAB1407430
Anti-EXOSC3 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
AV40824
Anti-EXOSC3 antibody produced in rabbit, IgG fraction of antiserum
HPA020485
Anti-EXOSC3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV37320
Anti-PYCARD antibody produced in rabbit, IgG fraction of antiserum
SAB1409624
Anti-S100A10 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA003340
Anti-S100A10 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
CKOZFN28012 CompoZr® Knockout ZFN Kit, Mouse Casp1 (NM_009807.2)
CKOZFND28012 CompoZr® Knockout ZFN Kit, ZFN plasmid only, Mouse Casp1 (NM_009807.2)
WH0051010M3
Monoclonal Anti-EXOSC3 antibody produced in mouse, clone 5C3, purified immunoglobulin, buffered aqueous solution
WH0006281M1
Monoclonal Anti-S100A10 antibody produced in mouse, clone 4D2-F1, purified immunoglobulin, buffered aqueous solution
SAB1404349
Monoclonal Anti-S100A10 antibody produced in mouse, clone 3E10, purified immunoglobulin, buffered aqueous solution
SAB5300380
Monoclonal Anti-S100A10 antibody produced in mouse, clone 4E7E10, ascites fluid
T1568 Thrombopoietin human, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture, ≥98% (SDS-PAGE and HPLC)