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

American Journal of Transplantation, vol. 21, pp. 993–1002

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.

Authors 7

1. Judith E. van Zanden corresponding

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

2. Neeltina M. Jager

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

3. Marc A. Seelen

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

4. Mohamed R. Daha Aachen Department of Nephrology, Leiden University Medical Center

   University Medical Center Groningen · University of Groningen · Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands

   Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

5. Zwanida J. Veldhuis

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

6. Henri G. D. Leuvenink

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands

7. Michiel Elardus Erasmus

   University Medical Center Groningen · University of Groningen

   Affiliation as printed

   Department of Cardiothoracic Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands