Pulmonary Transplantation: the role of brain death in donor lung injury

Avlonitis, Vassilios S.; Fisher, Andrew J.; Kirby, John A.; Dark, John H.

doi:10.1097/01.tp.0000066351.87480.9e

Cited by 199 publications

(133 citation statements)

References 87 publications

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“…In the present study, the two cardiac death donors did not receive MP but still had reduced numbers of CD16 + DC, indicating that factors other than the MP treatment cause the downregulation of CD16 in organ donors. We showed that changes in DC marker expression as observed in organ donor DC could be induced by activation in vitro, suggesting that brain death-associated inflammation (36,54,55) may similarly activate DC in vivo. Although activation markers were increased on organ donor spleen DC, their expression levels were lower than on fully activated DC.…”

Section: Discussionmentioning

confidence: 88%

Human Dendritic Cell Subsets from Spleen and Blood Are Similar in Phenotype and Function but Modified by Donor Health Status

Mittag

Proietto

Loudovaris

et al. 2011

The Journal of Immunology

206

195

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Mouse dendritic cells (DC) have been extensively studied in various tissues, especially spleen, and they comprise subsets with distinct developmental origins, surface phenotypes, and functions. Considerably less is known about human DC due to their rarity in blood and inaccessibility of other human tissues. The study of DC in human blood has revealed four subsets distinct in phenotype and function. In this study, we describe four equivalent DC subsets in human spleen obtained from deceased organ donors. We identify three conventional DC subsets characterized by surface expression of CD1b/c, CD141, and CD16, and one plasmacytoid DC subset characterized by CD304 expression. Human DC subsets in spleen were very similar to those in human blood with respect to surface phenotype, TLR and transcription factor expression, capacity to stimulate T cells, cytokine secretion, and cross-presentation of exogenous Ag. However, organ donor health status, in particular treatment with corticosteroid methylprednisolone and brain death, may affect DC phenotype and function. DC T cell stimulatory capacity was reduced but DC were qualitatively unchanged in methylprednisolone-treated deceased organ donor spleen compared with healthy donor blood. Overall, our findings indicate that human blood DC closely resemble human spleen DC. Furthermore, we confirm parallels between human and mouse DC subsets in phenotype and function, but also identify differences in transcription factor and TLR expression as well as functional properties. In particular, the hallmark functions of mouse CD8α+ DC subsets, that is, IL-12p70 secretion and cross-presentation, are not confined to the equivalent human CD141+ DC but are shared by CD1b/c+ and CD16+ DC subsets.

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Section: Discussionmentioning

confidence: 88%

Human Dendritic Cell Subsets from Spleen and Blood Are Similar in Phenotype and Function but Modified by Donor Health Status

Mittag

Proietto

Loudovaris

et al. 2011

The Journal of Immunology

206

195

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“…As evidenced by a large body of transplantation research, brain death has neurohumoral, metabolic, and inflammatory effects on the host (49)(50)(51)(52). It is likely that this physiologic state, in addition to inherent differences in the nondiseased lung across the study population, underlies the variability in expression observed for immune function genes.…”

Section: Discussionmentioning

confidence: 99%

Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung

Gruber

Coldren²,

Woolum³

et al. 2006

Am J Respir Cell Mol Biol

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Nondiseased tissue is an important reference for microarray studies of pulmonary disease. We obtained 23 single lungs from multiorgan donors at time of procurement. Donors varied in age, sex, smoking history, and ethnicity. Lungs were dissected into upper and lower lobe peripheral sections for RNA extraction. Microarray analysis was performed using Affymetrix Hu-133 Plus 2.0 arrays. We observed that the relative variability of gene expression increased rapidly from technical (lowest), to regional, to population (highest). In addition, age and sex have measurable effects on gene expression. Gene expression variability is heterogeneously distributed among biologic categories. We conclude that gene expression variability is greater between individuals than within individuals and that population variability is the most important factor in the study design of microarray experiments of the human lung. Classes of genes with high population variability are biologically important and provide a novel perspective into lung physiology and pathobiology. Our study represents the first comprehensive analysis of nondiseased lung tissue. The generation of this robust dataset has important implications for the design and implementation of future comparative expression analysis with pulmonary disease states.

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“…The lung is sensitive to the above changes (18). It is well recognized that massive sympathetic discharge resulting from a central nervous system insult, can cause neurogenic pulmonary edema (NPE) (19).…”

Section: Introductionmentioning

confidence: 99%

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

Avlonitis

Wigfield

Kirby

et al. 2005

American Journal of Transplantation

Self Cite

154

123

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Brain-dead donors are the major source of lungs for transplantation. Brain death is characterized by two hemodynamic phases. Initially, massive sympathetic discharge results in a hypertensive crisis. This is followed by neurogenic hypotension. Up-regulation of pro-inflammatory mediators occurs in all organs and lung injury develops; this can adversely affect graft function post-transplantation. The mechanisms of the systemic and lung inflammation are unknown. We hypothesized that the hemodynamic changes are responsible for these inflammatory phenomena. Brain death was induced by intra-cranial balloon inflation in rats. This resulted in hypertensive crisis, followed by hypotension. There was a significant increase in blood neutrophil CD11b/CD18 expression and pro-inflammatory cytokine levels in serum and bronchoalveolar lavage, compared with control animals. Rupture of the capillary-alveolar membrane was demonstrated by electron microscopy. Elimination of the hypertensive response by a -adrenergic antagonist pre-treatment prevented inflammatory lung injury, reduced the systemic inflammatory markers and preserved capillary-alveolar membrane integrity. Correction of the neurogenic hypotension with noradrenaline ameliorated the systemic inflammatory response and improved oxygenation. We conclude that the sympathetic discharge triggers systemic and lung inflammation, which can be further enhanced by neurogenic hypotension. Management of the brain-dead donor with early anti-inflammatory treatment and vasoconstrictors is warranted.

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Pulmonary Transplantation: the role of brain death in donor lung injury

Cited by 199 publications

References 87 publications

Human Dendritic Cell Subsets from Spleen and Blood Are Similar in Phenotype and Function but Modified by Donor Health Status

Human Dendritic Cell Subsets from Spleen and Blood Are Similar in Phenotype and Function but Modified by Donor Health Status

Human Lung Project: Evaluating Variance of Gene Expression in the Human Lung

The Hemodynamic Mechanisms of Lung Injury and Systemic Inflammatory Response Following Brain Death in the Transplant Donor

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