Connexin-43-dependent ATP release mediates macrophage activation during sepsis.

Michel Dosch, Joël Zindel, Fadi Jebbawi, Nicolas Melin, Daniel Sanchez-Taltavull, Deborah Stroka, Daniel Candinas & Guido Beldi
Bacterial spillage into a sterile environment following intestinal hollow-organ perforation leads to peritonitis and fulminant sepsis. Outcome of sepsis critically depends on macrophage activation by extracellular ATP-release and associated autocrine signalling via purinergic receptors. ATP-release mechanisms, however, are poorly understood. Here, we show that TLR-2 and -4 agonists trigger ATP-release via Connexin-43 hemichannels in macrophages leading to poor sepsis survival. In humans, Connexin-43 was upregulated on macrophages isolated from the peritoneal cavity in patients with...
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