Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury

• Published in: Blood Vol. 108; no. 7; pp. 2455 - 2462
• Main Authors: Khan, Samina Yasmin, Kelher, Marguerite R., Heal, Joanna M., Blumberg, Neil, Boshkov, Lynn K., Phipps, Richard, Gettings, Kelly F., McLaughlin, Nathan J., Silliman, Christopher C.
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01-10-2006; The Americain Society of Hematology; The American Society of Hematology
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; CD40 Antigens - biosynthesis; CD40 Ligand - chemistry; Cell Membrane - metabolism; Cells, Cultured; Cross-Linking Reagents - pharmacology; Endothelium, Vascular - cytology; Humans; Inflammation; Ligands; Lung - pathology; Lung Injury; Medical sciences; Neutrophils - metabolism; Pneumology; Respiratory system : syndromes and miscellaneous diseases; Transfusion Medicine; Transfusion Reaction; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Human; Respiratory disease; Pathogenesis; CD40 ligand; Granulocyte; Soluble form; Neutrophil; Cofactor; Transfusion related acute lung injury; Blood
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-04-017251

Transfusion-related acute lung injury (TRALI) is a form of posttransfusion acute pulmonary insufficiency that has been linked to the infusion of biologic response modifiers (BRMs), including antileukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived proinflammatory mediator that accumulates during platelet storage. We hypothesized that human polymorpho-nuclear leukocytes (PMNs) express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN-mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma, with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and packed red blood cells (PRBCs). PCs implicated in TRALI reactions contained significantly higher sCD40L levels than control PCs. PMNs express functional CD40 on the plasma membrane, and recombinant sCD40L (10 ng/mL-1 μg/mL) rapidly (5 minutes) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a 2-event in vitro model of TRALI. We concluded that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs, causing endothelial damage and possibly TRALI in predisposed patients.