Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 7, 2018; 24(45): 5131-5143
Published online Dec 7, 2018. doi: 10.3748/wjg.v24.i45.5131
Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages
Ruo-Hong Liu, Yi Wen, Hong-Yu Sun, Chun-Yu Liu, Yu-Fan Zhang, Yi Yang, Qi-Lin Huang, Jia-Jia Tang, Can-Chen Huang, Li-Jun Tang
Ruo-Hong Liu, Yi Wen, Hong-Yu Sun, Chun-Yu Liu, Yi Yang, Qi-Lin Huang, Can-Chen Huang, Li-Jun Tang, PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
Ruo-Hong Liu, Yi Wen, Li-Jun Tang, Third Military Medical University (Army Medical University), Chongqing 400037, China
Yu-Fan Zhang, Jiaotong Hospital Affiliated with the Sichuan Provincial People’s Hospital, Chengdu 611730, Sichuan Province, China
Jia-Jia Tang, Department of Ultrasound, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing 100032, China
Author contributions: Liu RH, Wen Y and Sun HY contributed equally to this work; Liu RH and Wen Y performed the majority of the experiments; Liu CY and Huang CC contributed to the animal experiments; Yang Y and Huang QL helped with the in vitro experiments; Zhang YF and Tang JJ contributed to data collection and manuscript preparation; Liu RH and Sun HY drafted the manuscript; and Tang LJ revised and approved the manuscript.
Supported by the National Natural Science Foundation of China, No. 81772001, No. 8177071311 and No. 81502696; the National Clinical Key Subject of China, No. 41792113; the Technology Plan Program of Sichuan Province, No. 2015SZ0229, No. 2018JY0041 and No. 18YYJC0442; and the Science and Technology Development Plan of Sichuan Province, No. 2016YJ0023.
Correspondence author to: Li-Jun Tang, MD, PhD, Chief Doctor, PLA Center for General Surgery and Pancreatic Injury and the Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, No. 270, Tianhui Road, Rongdu Avenue, Jinniu, Chengdu 610083, Sichuan Province, China.
Telephone: +86-28-86570265
Received: September 27, 2018
Peer-review started: September 27, 2018
First decision: October 14, 2018
Revised: October 20, 2018
Accepted: November 9, 2018
Article in press: November 9, 2018
Published online: December 7, 2018
Research background

Severe acute pancreatitis (SAP) is a highly lethal disease with limited therapeutic options and is characterized by a critical systemic inflammatory response. Pancreatitis-associated ascitic fluids (PAAF) play an important role in the pathogenesis of SAP because of the pro-inflammatory mediators the PAAF contain. Our previous studies suggested that APD ameliorates SAP by removing the PAAF. However, the mechanism underlying the success of APD treatment remains poorly understood. In the present study, we aimed to explore the possible mechanism by which APD ameliorates SAP.

Research motivation

The key issue in treating SAP is to control the activated inflammatory cascade and restore immune homeostasis. Peritoneal macrophages (PMs), crucial inflammatory cells in the abdominal cavity, are implicated in the initiation and progression of SAP in the early stage, and the function of PMs is regulated by the PAAF. In this study, we found that APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanisms underlying the therapeutic effect of APD.

Research objectives

The aim of this study was to determine the polarization phenotypes of PMs and the corresponding inflammatory responses in a rat model of SAP following APD treatment and to explore the possible mechanism by which APD treatment ameliorates SAP.

Research methods

The effect of APD on the polarization response of PMs was determined in an SAP rat model induced by 5% Na-taurocholate retrograde injection and in a peritoneal inflammatory environment simulated by adding peritoneal lavage to culture medium in vitro. HE staining and measurement of the levels of amylase, lipase, and inflammatory mediators were performed. The M1/M2 phenotype ratio of PMs was identified by flow cytometry and RT-PCR. The distribution of macrophages and their protein expression in the pancreas were determined by immunofluorescence staining and Western blot.

Research results

APD treatment ameliorates SAP by significantly reducing the pathological scores and the levels of amylase, lipase, tumor necrosis factor-α, and interleukin (IL)-1β. Importantly, APD treatment polarizes PMs towards the M2 phenotype and increases the anti-inflammatory mediators IL-4 and IL-10 in the peritoneal lavage. Furthermore, PMs exhibited a trend towards the M2 phenotype in a simulated peritoneal inflammatory environment in vitro. Finally, APD treatment increased the number of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP rats.

Research conclusions

APD treatment exerts anti-inflammatory effects by regulating the M2 polarization of PMs, providing novel insights into the mechanisms underlying its therapeutic effect.

Research perspectives

Our study provided evidence for the first time that APD ameliorates inflammation in rats with SAP by regulating PM M2 polarization. However, solid evidence that APD polarizes PMs to the M2 phenotype and the underlying molecular mechanism still need to be explored. Furthermore, future research should focus on the effect of M2 macrophages on immune homeostasis restoration and tissue repair in the injured pancreas.