title: 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.
abstract: 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 mug/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.
authors.affiliation: Bonfils Blood Center, 717 Yosemite St, Denver, CO 80230, USA.
authors.forename: Samina Yasmin
authors.initials: SY
authors.lastname: Khan
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Kelher
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Heal
authors.forename: Neil
authors.initials: N
authors.lastname: Blumberg
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Boshkov
authors.forename: Richard
authors.initials: R
authors.lastname: Phipps
authors.forename: Kelly F
authors.initials: KF
authors.lastname: Gettings
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: McLaughlin
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D019013:CD40 Antigens / Q000096:biosynthesis*; D023201:CD40 Ligand / Q000737:chemistry*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007249:Inflammation; D008024:Ligands; D008168:Lung / Q000473:pathology; D055370:Lung Injury; D009504:Neutrophils / Q000378:metabolism*; D065227:Transfusion Reaction
chemical_list: D019013:CD40 Antigens; D003432:Cross-Linking Reagents; D008024:Ligands; D023201:CD40 Ligand