SOCS3 Promotes the Activation of CCR2-Dependent Migratory Cd11b+GR-1lowly6chigh Macrophages in Murine Cerulein Pancreatitis

Abstract

mice followed by comparison of MFG-E8+/+ and MFG-E8-/mice for pathological changes in the pancreas. Typically, MFG-E8+/+ and MFG-E8-/mice (7 weeks, male) were subjected to ten injections of cerulein (50 μg/kg, i.p.) at hourly intervals. They were sacrificed at various time points after the final cerulein administration. We found that MFG-E8 deficiency did not affect the severity of acute phase of cerulein-induced pancreatitis. However, pancreatic recovery following cerulein-induced pancreatitis was markedly delayed in MFG-E8-/mice comparing to wild-type controls. Furthermore, we examined whether lack of MFG-E8 leads to progression of recurrent pancreatic injury to chronic inflammation. Briefly, MFG-E8-/and MFG-E8+/+ mice were respectively subjected to repeated courses of acute pancreatitis for two weeks. Control mice were treated with saline. Using histological examination, we revealed that wild-type mice recovered from repeated acute pancreatitis within 7 days after the final cerulein administration. In contrast, pancreas from MFG-E8-/displayed persistent inflammatory cell infiltration, disruption of acinar cells, and replacement of parenchymal tissues with collagen fibers and stromal cells. Together, the data suggest a central role for MFG-E8 in pancreatic recovery from pancreatitis. In conclusion, MFG-E8 deficiency impairs pancreatic recovery. This novel finding may provide a potential therapeutic target in the further development of novel molecular agents for patients with pancreatitis and pancreatic fibrosis.