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.