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Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells.

ABSTRACT: Graft rejection remains the major obstacle after vascularized solid organ transplantation. Endothelial cells, which form the interface between the transplanted graft and the host's immunity, are the first target for host immune cells. During acute cellular rejection endothelial cells are directly attacked by HLA I and II-recognizing NK cells, macrophages, and T cells, and activation of the complement system leads to endothelial cell lysis. The established forms of immunosuppressive therapy provide effective treatment options, but the treatment of chronic rejection of solid organs remains challenging. Chronic rejection is mainly based on production of donor-specific antibodies that induce endothelial cell activation-a condition which phenotypically resembles chronic inflammation. Activated endothelial cells produce chemokines, and expression of adhesion molecules increases. Due to this pro-inflammatory microenvironment, leukocytes are recruited and transmigrate from the bloodstream across the endothelial monolayer into the vessel wall. This mononuclear infiltrate is a hallmark of transplant vasculopathy. Furthermore, expression profiles of different cytokines serve as clinical markers for the patient's outcome. Besides their effects on immune cells, activated endothelial cells support the migration and proliferation of vascular smooth muscle cells. In turn, muscle cell recruitment leads to neointima formation followed by reduction in organ perfusion and eventually results in tissue injury. Activation of endothelial cells involves antibody ligation to the surface of endothelial cells. Subsequently, intracellular signaling pathways are initiated. These signaling cascades may serve as targets to prevent or treat adverse effects in antibody-activated endothelial cells. Preventive or therapeutic strategies for chronic rejection can be investigated in sophisticated mouse models of transplant vasculopathy, mimicking interactions between immune cells and endothelium.

SUBMITTER: Kummer L

PROVIDER: S-EPMC7227440 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells.

Kummer Laura L Zaradzki Marcin M Vijayan Vijith V Arif Rawa R Weigand Markus A MA Immenschuh Stephan S Wagner Andreas H AH Larmann Jan J

Frontiers in physiology 20200508

Graft rejection remains the major obstacle after vascularized solid organ transplantation. Endothelial cells, which form the interface between the transplanted graft and the host's immunity, are the first target for host immune cells. During acute cellular rejection endothelial cells are directly attacked by HLA I and II-recognizing NK cells, macrophages, and T cells, and activation of the complement system leads to endothelial cell lysis. The established forms of immunosuppressive therapy provi ...[more]

PMID: 32457653

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Project description:Background and purposePosterior reversible encephalopathy syndrome (PRES) is known to occur after solid organ transplantation (SOT), potentially associated with cyclosporine and tacrolimus. In this study, we assess the frequency and clinical and imaging characteristics of PRES after SOT.Materials and methodsWe identified 27 patients (13 men and 14 women; age range, 22-72 years) who developed PRES after SOT. Features noted included SOT subtype, incidence and timing of PRES, infection and rejection, mean arterial pressure (MAP), and toxicity brain edema.ResultsPRES developed in 21 (0.49%) of 4222 patients who underwent transplantation within the study period (no significant difference among SOT subtypes). Transplantation was performed in 5 patients before the study period, and 1 patient underwent transplantation elsewhere. In consideration of all 27 patients, PRES typically developed in the first 2 months in patients who had SOT of the liver (9 of 10 patients) and was associated with cytomegalovirus (CMV), mild rejection, or systemic bacterial infection. PRES also typically developed after 1 year in patients who had SOT of the kidney (8 of 9 patients) and was associated with moderate rejection or bacterial infection. Toxicity MAP was significantly lower (P < .001) in liver transplants (average MAP, 104.8 +/- 16 mm Hg) compared with that in kidney transplants (average MAP, 143 +/- 20 mm Hg). Toxicity brain edema was significantly greater (P < .001) in patients who had liver transplants and developed PRES compared with patients who had undergone kidney transplants despite severe hypertension in those who had the kidney transplants.ConclusionPatients who had undergone SOTs have a similar low incidence of developing PRES. Differences between those who have had liver and kidney transplants included time after transplant, toxicity MAP, and PRES vasogenic edema noted at presentation. In patients who have undergone kidney transplants, severely elevated MAP was associated with reduced, not greater, brain edema.

Dataset Information

Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells.

Publications

Vascular Signaling in Allogenic Solid Organ Transplantation - The Role of Endothelial Cells.

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