Journal of leukocyte biology
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Leukocyte infiltration and acinar cell necrosis are hallmarks of severe AP, but the signaling pathways regulating inflammation and organ injury in the pancreas remain elusive. In the present study, we investigated the role of geranylgeranyltransferase in AP. Male C57BL/6 mice were treated with a geranylgeranyltransferase inhibitor GGTI-2133 (20 mg/kg) prior to induction of pancreatitis by infusion of taurocholate into the pancreatic duct. ⋯ A significant role of geranylgeranyltransferase was confirmed in an alternate model of AP induced by L-arginine challenge. Our findings show that geranylgeranyltransferase regulates neutrophil accumulation and tissue damage via expression of Mac-1 on neutrophils and CXCL2 formation in AP. Thus, these results reveal new signaling mechanisms in pancreatitis and indicate that targeting geranylgeranyltransferase might be an effective way to ameliorate severe AP.