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

In brain-dead donors immunological activation occurs, which deteriorates donor lung quality. Whether the complement system is activated and which pathways are herein involved, remains unknown. We aimed to investigate whether 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 wildtype (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 reduced, as corroborated by influx of neutrophils and gene expressions of IL-6, IL-8-like KC, TNF-α, E-selectin and MCP-1. In C4-/- mice, complement was reduced on both systemic and local level. Thereby, 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.