Indirect antibody–mediated and antibody-independent mechanism of TRALI induction. Priming events secondary to underlying pulmonary pathology, often induced by LPS injection in experimental animal models, activate endothelial cells, resulting in significant sequestration of neutrophils within the pulmonary vasculature. After pulmonary priming events, transfusion-associated factors induce rapid intravascular neutrophil activation with subsequent endothelial damage, vascular compromise and pulmonary edema. Factors responsible for transfusion-induced activation are shown and include soluble CD40L, antibody-mediated monocyte activation and cytokine release, lipid mediators and impaired chemokine scavenging by aged red blood cells. Duffy antigens are specifically shown on the surface of red blood cells, where Duffy* on aged red blood cells indicates Duffy receptors with impaired capacity to bind intravascular chemokines.