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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
BACKGROUND
Acute pancreatitis (AP) is rapid-onset pancreatic inflammation that causes local and systemic inflammatory response syndrome (SIRS) with high morbidity and mortality, but no approved therapies are currently available. P-selectin glycoprotein ligand 1 (PSGL-1) is a transmembrane glycoprotein to initiate inflammatory responses. We hypothesized that PSGL-1 may be involved in the development of AP and would be a new target for the treatment of AP.
AIM
To investigate the role and mechanism of PSGL-1 in the development of AP.
METHODS
The PSGL-1 expression on leukocytes was detected in peripheral blood of AP patients and volunteers. Pancreatic injury, inflammatory cytokines expression, and inflammatory cell infiltration was measured in AP mouse models induced with PSGL-1 knockout (PSGL-1-/-) and wild-type (PSGL-1+/+) mice. Leukocyte-endothelial cell adhesion was measured in a peripheral blood mononuclear cell (PBMC)-endothelial cell coculture system.
RESULTS
The expression of PSGL-1 on monocytes and neutrophils was significantly increased in AP patients. Compared with PSGL-1+/+ mice, PSGL-1-/- AP mice induced by caerulein exhibited lower serum amylase, less Interleukin-1beta (IL-1beta) and Interleukin-6 (IL-6) expression, less neutrophil and macrophage infiltration, and reduced peripheral neutrophil and monocyte accounts. PSGL-1 deficiency alleviated leukocyte-endothelial cell adhesion via IL-6 but not IL-1beta.
CONCLUSION
PSGL-1 deficiency effectively inhibits the development of AP by preventing leukocyte-endothelial cell adhesion via IL-6 stimulation and may become a potential therapeutic target for treating AP.
Core Tip: The severity of acute pancreatitis (AP) is inversely related to the number of leukocytes that infiltrate pancreatic tissue. P-selectin glycoprotein ligand 1 (PSGL-1) plays an important role in the development of AP by promoting inflammatory cell infiltration initiated by leukocyte and endothelial cell adhesion. PSGL-1 deficiency may protect against the development of AP and may be a new potential target for AP therapy.
