Inhibition of the CD40/CD40L complex protects mice against ALI‐induced pancreas degradation

Abstract

BACKGROUND Acute lung injury (ALI) is a severe complication of transfusion. In a previous study, we saw that inhibition of the CD40/CD40L complex allowed restoration of ALI lesions in an experimental mouse model. OBJECTIVES This study focused on pancreas‐associated injury development during experimental ALI pathogenesis and its limitation through CD40/CD40L complex inhibition. MATERIALS AND METHODS An ALI mouse model was established through intraperitoneal lipopolysaccharide and intravenous anti–major histocompatibility complex class I monoclonal antibody injection. Preemption of lesions was achieved with intravenous injection of neutralizing anti‐CD40L monoclonal antibody 30 minutes before the trigger, that is, anti–major histocompatibility complex class I monoclonal antibody administration. Histology and immunoassay analyses were used to evaluate pancreatic lesions. RESULTS ALI development induced significant degradation of the lungs and pancreas and was associated with pancreatic lesions. Different scores were established showing more severe injury to the pancreas in ALI conditions; however, injury was significantly reduced through CD40/CD40L complex inhibition. CONCLUSION This study supports the idea that several organs are exposed during ALI development, and particularly when such experimental ALI aims at mimicking transfusion‐associated ALI; nevertheless, preventive treatment inhibiting CD40/CD40L (sCD40L) complex formation provides protection from lung disease as well as disease of other organs.

Platelets as Key Factors in Inflammation: Focus on CD40L/CD40

“…As both diseases, namely pancreatitis and TRALI, are closely linked, we investigated the involvement of the CD40L/CD40 protein interaction in the regulation of pancreatitis immediately following the onset of TRALI. Using an animal model of TRALI induced by successive injection of LPS and anti-CMH I antibodies and preventive treatment based on anti-CD40L antibodies, we were able to demonstrate that the pancreatic damage observed in our ALI model is prevented to a significant extent when the CD40L/CD40 immune complex is inhibited (166).…”