NoBlood

Jan B. Wade · #1 (**permalink**) 06-18-2006, 09:50 AM

Blood. 2006 Jun 13; [Epub ahead of print]

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.

Khan SY, Kelher MR, Heal JM, Blumberg N, Boshkov LK, Phipps R, Gettings KF, McLaughlin NJ, Silliman CC.

Department of Surgery, University of Schoollace> of Medicine, Denver, CO.

TRALI is a post-transfusion acute pulmonary insufficiency, which has been linked to the infusion of biological response modifiers (BRMs) including anti-leukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived pro-inflammatory mediator that accumulates during platelet storage. We hypothesize that human 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 PRBCs. PCs implicated in TRALI reactions contained significantly higher sCD40L levels as compared to control PCs. PMNs express functional CD40 on the plasma membrane and recombinant sCD40L [10 ng/ml-1 ; microg/ml] rapidly (5 min) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a two-event in vitro model of TRALI. We conclude that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs causing endothelial damage and may cause TRALI in predisposed patients.

NoBlood

TRALI-Soluble CD40 ligand accumulates in stored blood components, primes neutrophils