Leukadherin-1 mitigates disseminated intravascular coagulation in acute pancreatitis by suppressing necroptosis

Abstract

Disseminated intravascular coagulation (DIC) is a fatal complication of acute pancreatitis (AP), leading to multiple organ dysfunction syndrome (MODS), but its pathogenic mechanism is poorly understood. Here, we identify Leukadherin-1 (LA-1) as a potential therapeutic agent against AP-associated DIC. LA-1 effectively attenuated DIC progression by suppressing tissue factor (TF) release from necroptotic macrophages, achieved through inhibition of RIPK1 phosphorylation at Ser166—a critical step in necroptosis signaling pathways. Additionally, LA-1 inhibited necroptosis in pancreatic acinar cells, potentially disrupting macrophage necroptosis. These findings propose a novel approach to targeting the interplay between necroptosis and coagulation and provides valuable insights into potential therapeutic strategies for managing coagulation disorders associated with AP, thus alleviates the burden of this debilitating condition.