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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
P-selectin glycoprotein ligand 1 deficiency prevents development of acute pancreatitis by attenuating leukocyte infiltration
Xu Zhang, Ming Zhu, Xiao-Liang Jiang, Xing Liu, Xue Liu, Pan Liu, Xian-Xian Wu, Zhi-Wei Yang, Tao Qin
Xu Zhang, Tao Qin, Academy of Medical Sciences, Zhengzhou University, Zhengzhou 450003, Henan Province, China
Xu Zhang, Pan Liu, Tao Qin, Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s Hospital, Zhengzhou 450003, Henan Province, China
Ming Zhu, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510000, Guangdong Province, China
Xiao-Liang Jiang, Xing Liu, Xue Liu, Xian-Xian Wu, Zhi-Wei Yang, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical Collage (PUMC), Beijing 100021, China
Author contributions: Zhang X performed the majority of experiments; Zhu M was responsible for article correction; Jiang XL conducted the experimental analysis; Liu X provided vital reagents; Liu X established the AP mouse model; Wu XX analyzed the data and developed analysis tools; Liu P analyzed the clinical data; Yang ZW designed the research; Qin T supervised the research and provided financial support for this work; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81670387, No. 31671440, and No. 81800402.
Institutional review board statement: This study was reviewed and approved by Ethics Committee of People’s Hospital of Zhengzhou University.
Institutional animal care and use committee statement: The animal care and use were approved by the Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College.
Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any products, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Tao Qin, MD, PhD, Doctor, Professor, Department of Hepato-Biliary-Pancreatic Surgery, Zhengzhou University People’s Hospital & Henan Provincial People’s
Hospital, No. 7 Weiwu Road, Zhengzhou 450003, Henan Province, goodfreecn@163.com
Received: April 14, 2020
Peer-review started: April 14, 2020
First decision: April 26, 2020
Revised: July 13, 2020
Accepted: September 10, 2020
Article in press: September 10, 2020
Published online: November 7, 2020
Processing time: 205 Days and 17.2 Hours
ARTICLE HIGHLIGHTS
Research background
Acute pancreatitis (AP)-induced pancreatic injury is positively correlated with the degree of immune cell infiltration. P-selectin glycoprotein ligand 1 (PSGL-1) can regulate leukocyte activation and recruitment in various inflammation-related diseases. Our study showed that the expression of PSGL-1 in leukocytes of AP patients is increased. However, the underlying mechanism has not been fully elucidated.
Research motivation
Uncontrolled systemic inflammation in AP results in a high risk of morbidity and mortality, but no approved therapies are currently available. Elucidating the mechanism of action of PSGL-1 in AP is expected to help identify new targets for the treatment of pancreatitis.
Research objectives
This research aimed to investigate the role and mechanism of PSGL-1 in the inflammatory response during the development of AP.
Research methods
We used flow cytometry to detect the expression of PSGL-1 in leukocytes from AP patients and a mouse model of caerulein-induced AP. Next, PSGL-1-/- mice administered caerulein were used to detect pancreatic injury, inflammatory cytokine expression, and inflammatory cell infiltration. A peripheral blood mononuclear cell-endothelial cell coculture system was used to clarify the mechanism by which PSGL-1 regulates leukocyte adhesion to endothelial cells.
Research results
The results of this study indicated that the numbers of monocytes and neutrophils and the expression of PSGL-1 in the peripheral blood of patients were significantly increased. PSGL-1 deficiency reduced serum amylase levels, the expression of IL-1beta and IL-6 in the serum and pancreas, the number of infiltrated neutrophils and macrophages in the pancreas, and the number of peripheral circulating neutrophils and monocytes in the AP mouse model. PSGL-1 deficiency alleviated caerulein-induced leukocyte-endothelial cell adhesion.
Research conclusions
PSGL-1 deficiency protects against the development of AP by inducing leukocyte-endothelial cell adhesion.
Research perspectives
Further research will explore the effect of PSGL-1 on leukocyte function and treatments for AP involving drugs targeting PSGL-1.
