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      Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages

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          Abstract

          AIM

          To investigate the role of peritoneal macrophage (PM) polarization in the therapeutic effect of abdominal paracentesis drainage (APD) on severe acute pancreatitis (SAP).

          METHODS

          SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.

          RESULTS

          APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin (IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of pro-inflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1 in the pancreas of SAP model rats.

          CONCLUSION

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

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          Most cited references24

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          Role of Human Macrophage Polarization in Inflammation during Infectious Diseases

          Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). This review brews the complexity of the situation during infectious diseases by stressing on this continuum between M1-like and M2-like extremes. We first discuss the basic biology of macrophage polarization, function, and role in the inflammatory process and its resolution. Secondly, we discuss the relevance of the macrophage polarization continuum during infectious and neglected diseases, and the possibility to interfere with such activation states as a promising therapeutic strategy in the treatment of such diseases.
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            Acute Pancreatitis.

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              The Role of Macrophage Polarization in Infectious and Inflammatory Diseases

              Macrophages, found in circulating blood as well as integrated into several tissues and organs throughout the body, represent an important first line of defense against disease and a necessary component of healthy tissue homeostasis. Additionally, macrophages that arise from the differentiation of monocytes recruited from the blood to inflamed tissues play a central role in regulating local inflammation. Studies of macrophage activation in the last decade or so have revealed that these cells adopt a staggering range of phenotypes that are finely tuned responses to a variety of different stimuli, and that the resulting subsets of activated macrophages play critical roles in both progression and resolution of disease. This review summarizes the current understanding of the contributions of differentially polarized macrophages to various infectious and inflammatory diseases and the ongoing effort to develop novel therapies that target this key aspect of macrophage biology.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                7 December 2018
                7 December 2018
                : 24
                : 45
                : 5131-5143
                Affiliations
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                Third Military Medical University (Army Medical University), Chongqing 400037, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                Third Military Medical University (Army Medical University), Chongqing 400037, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                Jiaotong Hospital Affiliated with the Sichuan Provincial People’s Hospital, Chengdu 611730, Sichuan Province, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                Department of Ultrasound, Chinese Academy of Medical Sciences and Peking Union Medical College Hospital, Beijing 100032, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province, Chengdu Military General Hospital, Chengdu 610083, Sichuan Province, China
                Third Military Medical University (Army Medical University), Chongqing 400037, China. tanglj2016@ 123456163.com
                Author notes

                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. tanglj2016@ 123456163.com

                Telephone: +86-28-86570265

                Article
                jWJG.v24.i45.pg5131
                10.3748/wjg.v24.i45.5131
                6288649
                30568390
                f4b7220f-d14c-4ead-8709-1b0b2d4f7cc2
                ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 27 September 2018
                : 20 October 2018
                : 9 November 2018
                Categories
                Basic Study

                abdominal paracentesis drainage,peritoneal macrophages,polarization,severe acute pancreatitis

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