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
Processing time: 205 Days and 17.2 Hours
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.
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.
This research aimed to investigate the role and mechanism of PSGL-1 in the inflammatory response during the development of AP.
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.
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.
PSGL-1 deficiency protects against the development of AP by inducing leukocyte-endothelial cell adhesion.
Further research will explore the effect of PSGL-1 on leukocyte function and treatments for AP involving drugs targeting PSGL-1.