Extracellular release of ATP promotes systemic inflammation during acute pancreatitis.

In the current study, we explored the role of extracellular ATP (eATP) in promoting systemic inflammation during development of acute pancreatitis (AP). Release of eATP was evaluated in plasma and bronchoalveolar lavage fluid (BALF) of mice with experimental AP. Prophylactic intervention using apyrase or suramin was used to understand the role and contribution of eATP in pancreatitis-associated systemic injury. AP of varying severity was induced in C57BL/6 mice by one-day or 2-day caerulein, caerulein + LPS and L-arginine models. eATP was measured in plasma and BALF. Mice were treated with either suramin or apyrase in the caerulein and L-arginine models of AP. Plasma cytokines, lung and pancreatic MPO; morphometric analysis of pancreatic and lung histology, were used to assess the severity of pancreatitis. Plasma eATP and P2 receptors in pancreas and lungs were significantly elevated in the experimental models of AP. Blocking the effect of eATP by suramin led to reduced levels of plasma IL-6 and TNF-α as well as reduced lung, and pancreatic injury. Neutralizing eATP with apyrase reduced systemic injury, but did not ameliorate local injury. The results of this study support the role of eATP and P2 receptors in promoting systemic inflammation during AP. Modulating purinergic signaling during AP can be an important therapeutic strategy in controlling systemic inflammation and thus, SIRS during AP.