Published online Nov 7, 2020. doi: 10.3748/wjg.v26.i41.6361
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
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.
To investigate the role and mechanism of PSGL-1 in the development of AP.
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.
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.
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.