ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages

Gizem Ayna, Dmitri V. Krysko, Agnieszka Kaczmarek, G. Petrovski, Peter Vandenabeele, L. Fésüs

Research output: Contribution to journalArticle

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Abstract

Pathogen-activated and damage-associated molecular patterns activate the inflammasome in macrophages. We report that mouse macrophages release IL-1β while co-incubated with pro-B (Ba/F3) cells dying, as a result of IL-3 withdrawal, by apoptosis with autophagy, but not when they are co-incubated with living, apoptotic, necrotic or necrostatin-1 treated cells. NALP3-deficient macrophages display reduced IL-1β secretion, which is also inhibited in macrophages deficient in caspase-1 or pre-treated with its inhibitor. This finding demonstrates that the inflammasome is activated during phagocytosis of dying autophagic cells. We show that activation of NALP3 depends on phagocytosis of dying cells, ATP release through pannexin-1 channels of dying autophagic cells, P2X7 purinergic receptor activation, and on consequent potassium efflux. Dying autophagic Ba/F3 cells injected intraperitoneally in mice recruit neutrophils and thereby induce acute inflammation. These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses.

Original languageEnglish
Article numbere40069
JournalPLoS One
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 29 2012

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Inflammasomes
macrophage activation
Cytophagocytosis
Macrophage Activation
Macrophages
phagocytosis
Adenosine Triphosphate
Chemical activation
macrophages
Interleukin-1
cells
interleukin-1
Purinergic P2X7 Receptors
Caspase 1
mice
Interleukin-3
inflammation
Pathogens
interleukin-3
caspase-1

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. / Ayna, Gizem; Krysko, Dmitri V.; Kaczmarek, Agnieszka; Petrovski, G.; Vandenabeele, Peter; Fésüs, L.

In: PLoS One, Vol. 7, No. 6, e40069, 29.06.2012.

Research output: Contribution to journalArticle

Ayna, Gizem ; Krysko, Dmitri V. ; Kaczmarek, Agnieszka ; Petrovski, G. ; Vandenabeele, Peter ; Fésüs, L. / ATP release from dying autophagic cells and their phagocytosis are crucial for inflammasome activation in macrophages. In: PLoS One. 2012 ; Vol. 7, No. 6.
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