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

Samina Yasmin Khan, Marguerite R. Kelher, Joanna M. Heal, Neil Blumberg, Lynn Boshkov, Richard Phipps, Kelly F. Gettings, Nathan J. McLaughlin, Christopher C. Silliman

Research output: Contribution to journalArticle

283 Citations (Scopus)

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 polymorphonuclear 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.

Original languageEnglish (US)
Pages (from-to)2455-2462
Number of pages8
JournalBlood
Volume108
Issue number7
DOIs
StatePublished - Oct 1 2006
Externally publishedYes

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CD40 Ligand
Acute Lung Injury
Platelets
Neutrophils
Blood
Blood Platelets
Endothelial cells
Cytotoxicity
Lung
Endothelial Cells
Blood Component Removal
Level control
Cell membranes
Ligation
Oxidoreductases
Erythrocytes
Cells
Cell Membrane
Lipids
Plasmas

ASJC Scopus subject areas

  • Hematology

Cite this

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, Samina Yasmin; Kelher, Marguerite R.; Heal, Joanna M.; Blumberg, Neil; Boshkov, Lynn; Phipps, Richard; Gettings, Kelly F.; McLaughlin, Nathan J.; Silliman, Christopher C.

In: Blood, Vol. 108, No. 7, 01.10.2006, p. 2455-2462.

Research output: Contribution to journalArticle

Khan, SY, Kelher, MR, Heal, JM, Blumberg, N, Boshkov, L, Phipps, R, Gettings, KF, McLaughlin, NJ & Silliman, CC 2006, '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', Blood, vol. 108, no. 7, pp. 2455-2462. https://doi.org/10.1182/blood-2006-04-017251
Khan, Samina Yasmin ; Kelher, Marguerite R. ; Heal, Joanna M. ; Blumberg, Neil ; Boshkov, Lynn ; Phipps, Richard ; Gettings, Kelly F. ; McLaughlin, Nathan J. ; Silliman, Christopher C. / 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. In: Blood. 2006 ; Vol. 108, No. 7. pp. 2455-2462.
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AU - Khan, Samina Yasmin

AU - Kelher, Marguerite R.

AU - Heal, Joanna M.

AU - Blumberg, Neil

AU - Boshkov, Lynn

AU - Phipps, Richard

AU - Gettings, Kelly F.

AU - McLaughlin, Nathan J.

AU - Silliman, Christopher C.

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N2 - 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 polymorphonuclear 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.

AB - 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 polymorphonuclear 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.

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