دورية أكاديمية
أعرض في EDS

Brain Death Enhances Activation of the Innate Immune System and Leads to Reduced Renal Metabolic Gene Expression.

التفاصيل البيبلوغرافية
العنوان: Brain Death Enhances Activation of the Innate Immune System and Leads to Reduced Renal Metabolic Gene Expression.
المؤلفون: Zitur LJ; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Chlebeck PJ; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Odorico SK; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Danobeitia JS; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Zens TJ; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Van Kooten C; Department of Nephrology, Leiden University Medical Centre, Leiden, Netherlands., Eerhart M; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Reyes JA; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Springer ML; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Coonen JM; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI., Brunner KG; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI., Capuano SV; Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI., D'Alessandro AM; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI., Fernandez LA; Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI.
المصدر: Transplantation [Transplantation] 2019 Sep; Vol. 103 (9), pp. 1821-1833.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0132144 Publication Model: Print Cited Medium: Internet ISSN: 1534-6080 (Electronic) Linking ISSN: 00411337 NLM ISO Abbreviation: Transplantation Subsets: MEDLINE
أسماء مطبوعة: Publication: Hagerstown, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Williams & Wilkins.
مواضيع طبية MeSH: Brain Death/*immunology , Brain Death/*metabolism , Energy Metabolism/*genetics , Immunity, Innate/*genetics , Inflammation/*immunology , Inflammation/*metabolism , Kidney/*metabolism, Animals ; Biomarkers/blood ; Blood Coagulation/genetics ; Blood Coagulation Factors/genetics ; Blood Coagulation Factors/metabolism ; Complement Activation/genetics ; Critical Care ; Cytokines/blood ; Cytokines/genetics ; Disease Models, Animal ; Gene Expression Regulation ; Inflammation/blood ; Inflammation/genetics ; Macaca mulatta ; Time Factors
مستخلص: Background: Brain death (BD)-associated inflammation has been implicated in decreased kidney allograft function and survival, but the underlying mechanisms have not been well distinguished from the conditions of critical care itself. We have developed a clinically translatable model to separate and investigate strategies to improve donor management and critical care.
Methods: Brain-dead (n = 12) and sham (n = 5) rhesus macaques were maintained for 20 hours under intensive care unit-level conditions. Samples were collected for immunophenotyping, analysis of plasma proteins, coagulation studies, and gene analysis for changes in immune and metabolic profile with comparison to naive samples (n = 10).
Results: We observed an increase in circulating leukocytes and cytokines, activation of complement and coagulation pathways, and upregulation of genes associated with inflammation in both brain-dead and sham subjects relative to naïve controls. Sham demonstrated an intermediate phenotype of inflammation compared to BD. Analysis of gene expression in kidneys from BD kidneys revealed a similar upregulation of inflammatory profile in both BD and sham subjects, but BD presented a distinct reduction in metabolic and respiratory processes compared to sham and naïve kidneys.
Conclusion: BD is associated with activation of specific pathways of the innate immune system and changes to metabolic gene expression in renal tissue itself; however, sham donors presented an intermediate inflammatory response attributable to the critical care environment. The early onset and penetrating impact of this inflammatory response underscores the need for early intervention to prevent perioperative tissue injury to transplantable organs.
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معلومات مُعتمدة: R01 AI110617 United States AI NIAID NIH HHS; T32 AI125231 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (Biomarkers)
0 (Blood Coagulation Factors)
0 (Cytokines)
تواريخ الأحداث: Date Created: 20190410 Date Completed: 20200608 Latest Revision: 20200901
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6713605
DOI: 10.1097/TP.0000000000002744
PMID: 30964836
قاعدة البيانات: MEDLINE
الوصف
تدمد:1534-6080
DOI:10.1097/TP.0000000000002744