In the current study, we explored the role of extracellular ATP (eATP) in promoting systemic inflammation during development of acute pancreatitis (AP). Release of extracellular (e)ATP was evaluated in plasma and bronchoalveolar lavage fluid (BALF) of mice with experimental acute pancreatitis (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 using 1-day or 2-day caerulein, caerulein + LPS and L-arginine models. eATP was measured in plasma and BALF. Mice were treated with suramin or apyrase in the caerulein and L-arginine models of AP. Plasma cytokines, lung, and pancreatic myeloperoxidase, and morphometric analysis of pancreatic and lung histology, were used to assess the severity of pancreatitis. Plasma eATP and purinergic 2 (P2) receptors in the 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 TNFα 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, systemic inflammatory response syndrome during AP.
|Original language||English (US)|
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|State||Published - Oct 2019|
Bibliographical noteFunding Information:
This work was supported, in whole or in part, by National Institute of Diabetes and Digestive and Kidney Diseases Grants RO1 DK-058694, DK-092145, and R01 DK-093047 (to A. K. Saluja) and RO1 DK-111834 (to V. Dudeja).
© 2019 American Physiological Society. All rights reserved.
- Acute pancreatitis
- Lung injury
- P2 receptors
- Systemic inflammation