Brain death-induced lung injury is complement dependent, with a primary role for the classical/lectin pathway

Judith E. van Zanden*, Neeltina M. Jager, Marc A. Seelen, Mohamed R. Daha, Zwanida J. Veldhuis, Henri G. D. Leuvenink, Michiel E. Erasmus

*Corresponding author for this work

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Abstract

In brain-dead donors immunological activation occurs, which deteriorates donor lung quality. Whether the complement system is activated and which pathways are herein involved, remain unknown. We aimed to investigate whether brain death (BD)-induced lung injury is complement dependent and dissected the contribution of the complement activation pathways. BD was induced and sustained for 3 hours in wild-type (WT) and complement deficient mice. C3−/− mice represented total complement deficiency, C4−/− mice represented deficiency of the classical and lectin pathway, and factor properdin (P)−/− mice represented alternative pathway deficiency. Systemic and local complement levels, histological lung injury, and pulmonary inflammation were assessed. Systemic and local complement levels were reduced in C3−/− mice. In addition, histological lung injury and inflammation were attenuated, as corroborated by influx of neutrophils and gene expressions of interleukin (IL)-6, IL-8–like KC, TNF-α, E-selectin, and MCP-1. In C4−/− mice, complement was reduced on both systemic and local levels and histological lung injury and inflammatory status were ameliorated. In P−/− mice, histological lung injury was attenuated, though systemic and local complement levels, IL-6 and KC gene expressions, and neutrophil influx were not affected. We demonstrated that BD-induced lung injury is complement dependent, with a primary role for the classical/lectin activation pathway.

Original languageEnglish
Pages (from-to)993-1002
Number of pages10
JournalAmerican Journal of Transplantation
Volume21
Issue number3
Early online date4-Sep-2020
DOIs
Publication statusPublished - Mar-2021

Keywords

  • basic (laboratory) research
  • science
  • complement biology
  • donors and donation
  • donation after brain death (DBD)
  • immunosuppression
  • immune modulation
  • lung transplantation
  • pulmonology
  • translational research
  • CHRONIC REJECTION
  • ACTIVATION
  • C3
  • TRANSPLANTATION
  • IMMUNOLOGY
  • PROTEINS
  • DONORS
  • MODEL

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