[Ca2+]i Oscillations and @entity777 Release Induced by a-Hemolysin from XXXX Require P2 Receptor Activation in Renal Epithelia.

@entity8 @entity19 @entity34585 @entity2348 @entity777 @entity293 @entity526
@entity293 are commonly caused by a-hemolysin (HlyA)-producing @entity526 . In erythrocytes, the cytotoxic effect of HlyA is strongly amplified by P2X receptors, which are activated by extracellular ATP released from the cytosol of the erythrocytes. In @entity8 , HlyA causes reversible [Ca(2+)]i oscillations, which trigger interleukin-6 ( @entity777 ) and IL-8 release. We speculate that this effect is caused by HlyA-induced ATP release from the epithelial cells and successive P2 receptor activation. Here, we demonstrate that HlyA-induced [Ca(2+)]i oscillations in @entity8 were completely prevented by scavenging extracellular ATP. In accordance, HlyA was unable to inflict any [Ca(2+)]i oscillations in 132-1N1 cells, which lack P2R completely. After transfecting these cells with the hP2Y2 receptor, HlyA readily triggered [Ca(2+)]i oscillations, which were abolished by P2 receptor antagonists. Moreover, HlyA-induced [Ca(2+)]i oscillations were markedly reduced in medullary thick ascending limbs isolated from @entity34585 receptor-deficient @entity19 compared with wild type. Interestingly, the following HlyA-induced @entity777 release was absent in @entity34585 receptor-deficient @entity19 . This suggests that HlyA induces ATP release from @entity8 , which via @entity34585 receptors is the main mediator of HlyA-induced [Ca(2+)]i oscillations and @entity777 release. This supports the notion that ATP signaling occurs early during @entity2348 and is a key player in the further inflammatory response.
