TRALI is due to pulmonary venule damage from leucocytes with cholesterol crystal formation

Jensen, Hanne M.; Galante, Joseph M.; Kysar, Patricia; Tolstikov, Vladimir; Reddy, K. J.; Holland, Paul V.

doi:10.1111/j.1423-0410.2009.01235.x

Cited by 8 publications

(9 citation statements)

References 32 publications

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“…33 In another series of 3 fatal cases of immune-mediated TRALI, the autopsy demonstrated pulmonary edema with cholesterol crystals in the endothelial membranes of venules. 34 In this series, patient 1 had HLA class I A2 antigen corresponding to the donor's antibodies; in case 2, no WBC antibodies were identified in the donor, and in case 3 the donor had antibodies to HNA-3a. The proposed pathogenesis based on these findings is that WBCs are coated with antibodies then attached to the pulmonary venule endothelium where WBCs are activated.…”

Section: Incidence Outcome and Blood Component Associationmentioning

confidence: 99%

Transfusion-related acute lung injury: from bedside to bench and back

Shaz

Stowell

Hillyer

2011

Blood

108

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Over the past 60 years, the transfusion medicine community has attained significant knowledge regarding transfusionrelated acute lung injury (TRALI) through the bedside to bench and back to the bedside model. First, at the bedside, TRALI causes hypoxia and noncardiogenic pulmonary edema, typically within 6 hours of transfusion. Second, bedside studies showed a higher incidence in plasma and platelet products than in red blood cell products (the fatal TRALI incidence for plasma is 1:2-300 000 products; platelet, 1:3-400 000; red blood cells, 1:25 002 000), as well as an association with donor leukocyte antibodies (ϳ 80% of cases). Third, at the bench, antibodydependent and antibody-independent mechanisms have been described, requiring neutrophil and pulmonary endothelial cell activation. Antibodies, as well as alternate substances in blood products, result in neutrophil activation, which, in a susceptible patient, result in TRALI (2-hit hypothesis). Fourth, back to the bedside, policy changes based on results of these studies, such as minimizing use of plasma and platelet products from donors with leukocyte antibodies, have decreased the incidence of TRALI. Thus, steps to mitigate TRALI are in place, but a complete mechanistic understanding of the pathogenesis of TRALI and of which patients are at highest risk remains to be eluci-

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Section: Incidence Outcome and Blood Component Associationmentioning

confidence: 99%

Transfusion-related acute lung injury: from bedside to bench and back

Shaz

Stowell

Hillyer

2011

Blood

108

View full text Add to dashboard Cite

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Section: Discussionmentioning

confidence: 86%

“…1 By SEM and GC-MS, we showed that intravascular, extracellular cholesterol crystals were associated with these endothelial tears to which the pulmonary edema was attributed. 1 We now report a new finding discovered by TEM: crystals within neutrophils. Our modified hypothesis is that cholesterol crystals initially form within degranulated neutrophils, some crystals escape into the pulmonary capillaries, and the majority of crystals, in attached neutrophils, tear through the postcapillary venules with extravasation of plasma, causing the clinical condition known as TRALI.…”

Section: Discussionmentioning

confidence: 86%

“…9 We previously demonstrated by SEM and GC-MS that 2 fatal cases of TRALI showed extensive endothelial injury of pulmonary venules associated with cholesterol crystals ❚Image 1❚. 1 In experimental animal models, injection of cholesterol crystals has been demonstrated to injure the delicate endothelial cells of vessels by their extremely sharp and jagged geometric shape. Such animal studies also show that the injured blood vessels display diminished vasomotor function.…”

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confidence: 99%

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Neutrophils Contain Cholesterol Crystals in Transfusion-Related Acute Lung Injury (TRALI)

Ness

Jensen

Adamson

et al. 2013

American Journal of Clinical Pathology

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“…For example, two recent studies reported that cholesterol crystal accumulation in neutrophils, and secondarily, in endothelial cells, may underlie the pathogenesis of transfusion-related acute lung injury [43]. …”

Section: Cholesterol Impacts Neutrophil Functionmentioning

confidence: 99%

Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense

Gabor¹,

Fessler

2017

CMP

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It has become increasingly recognized that cholesterol and lipoproteins play significant roles in both lung physiology and the innate immune response. It is now known that the innate immune response and the cholesterol biosynthesis/trafficking network regulate one another, with important implications for pathogen invasion and host defense. The activation of pathogen recognition receptors and downstream cellular host defense functions are critically sensitive to cellular cholesterol. Conversely, microorganisms can co-opt the sterol/lipoprotein network in order to facilitate their own replication. Given that over 50% of adults in the U.S. have cholesterol abnormalities and pneumonia remains a leading cause of death, the potential impact of cholesterol on pulmonary host defense is of tremendous public health significance. This review addresses the emerging link between the innate immune response and sterol homeostasis, with a focus upon implications for respiratory infection. Clinical translations, including in the area of potential therapeutic development for infectious lung disease, are also discussed.

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TRALI is due to pulmonary venule damage from leucocytes with cholesterol crystal formation

Abstract: Pulmonary damage in TRALI is related to formation of cholesterol crystals that appear to pierce endothelial membranes of venules. The endothelial defects lead to plasma extravasation into the alveoli causing TRALI.

Cited by 8 publications

References 32 publications

Transfusion-related acute lung injury: from bedside to bench and back

Transfusion-related acute lung injury: from bedside to bench and back

Neutrophils Contain Cholesterol Crystals in Transfusion-Related Acute Lung Injury (TRALI)

Roles of the Mevalonate Pathway and Cholesterol Trafficking in Pulmonary Host Defense

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