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

Transfusion. 2019 Mar;59(3):1090-1101. doi: 10.1111/trf.15206. Epub 2019 Feb 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / immunology
  • Acute Lung Injury / metabolism*
  • Animals
  • CD40 Antigens / immunology
  • CD40 Antigens / metabolism*
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism*
  • Lipopolysaccharides / toxicity
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pancreas / immunology
  • Pancreas / metabolism*

Substances

  • CD40 Antigens
  • Lipopolysaccharides
  • CD40 Ligand