FIBRINOGEN-LIKE PROTEIN 2 PROTECTS THE AGGRAVATION OF HYPERTRIGLYCERIDEMIA ON THE SEVERITY OF HYPERTRIGLYCERIDEMIA ACUTE PANCREATITIS BY REGULATING MACROPHAGES.

Objective

The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP.

Methods

Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay. Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163.

Results

The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression.

Conclusion

FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.