scholarly journals The Evolving Roles of Macrophages in Organ Transplantation

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Junhui Li ◽  
Cai Li ◽  
Quan Zhuang ◽  
Bo Peng ◽  
Yi Zhu ◽  
...  

Organ transplantation is a life-saving strategy for patients with end-stage organ failure. Over the past few decades, organ transplantation has achieved an excellent success in short-term survival but only a marginal improvement in long-term graft outcomes. The pathophysiology of graft loss is multifactorial and remains incompletely defined. However, emerging evidence suggests macrophages as crucial mediators of acute and chronic allograft immunopathology. In this process, macrophage-mediated mobilization of first-line defenses, particularly phagocytosis and the release of acute inflammatory mediators, is important, but macrophages also launch adaptive alloimmune reactions against grafts through antigen processing and presentation, as well as providing costimulation. Additionally, crosstalk with other immune cells and graft endothelial cells causes tissue damage or fibrosis in transplanted organs, contributing to graft loss or tolerance resistance. However, some macrophages function as regulatory cells that are capable of suppressing allogeneic T cells, inhibiting DC maturation, inducing the differentiation of Tregs, and subsequently promoting transplant tolerance. This functional diversity of macrophages in organ transplantation is consistent with their heterogeneity. Although our knowledge of the detrimental or beneficial effects of macrophages on transplants has exponentially increased, the exact mechanisms controlling macrophage functions are not yet completely understood. Here, we review recent advances in our understanding of the multifaceted nature of macrophages, focusing on their evolving roles in organ transplantation and the mechanisms involved in their activation and function in allograft transplantation. We also discuss potential therapeutic options and opportunities to target macrophage to improve the outcomes of transplant recipients.

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
G Valdi ◽  
G Varadi ◽  
A Panzera ◽  
M Parpinel ◽  
R Peressutti

Abstract Problem When WHO declared COVID-19 “international”, it was important not to damage some critical patients who need emergency procedures like organ transplantation, due to end stage organ disease. In 2003 SARS outbreak demonstrated the vulnerability of organ transplantation services o network. Descritption If transplantation is required as a life-saving procedure, it can be conducted with appropriate risk infection assessment. It is crucial during these emergencies to assess donor pool, as it is expected to decrease. A crucial point is to organize and evaluate the surge capacity, in terms of understaffing and lack of supplies, especially in ICU. The research methods were literature review using Pub Med, CDC, ECDC, WHO, TTS, searching as key words “SARS-CoV-2”, “COVID-19”, “transplantation”, “preparedness”. The analysis has been conducted between Feb 26th 2020 and March 5th 2020. Results As happened during SARS breakout in 2003, it is essential to establish a task force for crisis, currently updated and skilled for this particular management. Preparedness should regard especially the adoption of donor safety assessment procedures, ICU capability, the availability of covid-19 test for all the donors, and the adoption of specific post-transplant care. It is essential in this case establish preparedness in several points: education and training of the staff, practice drills, inspection of supplies, evaluation of surge capacity, relocation of patients. Lessons SARS-CoV-2 imposed in public health to establish new protocols and guidelines, which should be regularly updated to be useful in other epidemics outbreaks or other emergency situation. These protocols should focus on donor pool and ICU capability in order to carry on transplantation activities. Key messages This outbreak has tested the resilience of the whole system by day-by-day updating for transplantation teams and preparedness of the staff involved in transplantation management. During outbreak, seems to be useful a task force for crisis in order to support organ transplantation services.


2020 ◽  
Vol 21 (22) ◽  
pp. 8549
Author(s):  
André Renaldo Fernández ◽  
Rodrigo Sánchez-Tarjuelo ◽  
Paolo Cravedi ◽  
Jordi Ochando ◽  
Marcos López-Hoyos

Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.


2018 ◽  
Vol 159 (46) ◽  
pp. 1891-1897
Author(s):  
János Fazakas ◽  
Anikó Smudla

Abstract: One of the most prominent results of our age is organ transplantation, the single treatment option for patients with end-stage organ failure. The success of transplants depends on the donor care, the patient preoperative preassessment, the perioperative care of organ transplantation and aftercare. Successful transplantation therefore requires a prominent level of continuous collaboration between the surgeon, anaesthesiologist, radiologist, internal medicine and hepatologist, laboratory physician and almost all their associates. The complex interdisciplinary approach based on the research results can be used to improve the patient’s condition through pharmacotherapy, physiotherapy and psychotherapy during the time spent on waiting lists. The emergence of more active, targeted therapeutic options in perioperative graft resuscitation may help the currently inferior quality transplantable grafts or resuscitation out (machine perfusion) or in the recipient, thereby increasing the number of liver transplants. Deeper knowledge of hemostatic processes, along with the development of surgical techniques, would increase the number of blood transplant free transplants, thus improving the long-term survival of grafts. The present study aims at presenting the anaesthesia and early intensive therapy aspects of liver transplantation from aptitude assessment, through anaesthesia to early intensive therapeutic treatment. Orv Hetil. 2018; 159(46): 1891–1897.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoxiao Du ◽  
Weitao Que ◽  
Xin Hu ◽  
Xiao Yu ◽  
Wen-Zhi Guo ◽  
...  

BackgroundOridonin (Ori), the main bioactive ingredient of the natural anti-inflammatory herb Rabdosia rubescens, could be a covalent inhibitor of the NLRP3 inflammasome. Solid organ transplantation provides a life-saving optional therapy for patients with end-stage organ dysfunction. The long-term survival of solid organ transplantation remains restricted because of the possibility of rejection and the toxicity, infection, cardiovascular disease, and malignancy related to immunosuppressive (IS) drugs. However, the pathogenic mechanisms involved remain unclear. The ideal IS drugs to prevent allograft rejection have not been identified. Here, we investigated whether Ori could prolong the in vivo survival of completely mismatched cardiac allografts.MethodsThe cardiac transplantation models were conducted among three groups of mice from C57BL/6NCrSlc (B6/N) or C3H/HeNSlc (C3H) to C3H: the syngeneic and the allogeneic group, whose recipients were treated with vehicle of Ori, and the Ori treatment group, in which the recipients were transplanted hearts from MHC-I mismatched donors and treated with different dosages of Ori from post-operative day (POD) 0 to 7. Then, we investigated the effect of Ori on bone marrow-derived dendritic cell (BMDC) and allogeneic mixed lymphocyte reaction in vitro.ResultsOri with 3, 10, and 15 mg/kg Ori could prolong the survival (MST = 22.8, 49.2, and 65.3 days, respectively). We found that infiltrating CD8+ T cells and macrophages were decreased, and regulatory T cells (Tregs) were expanded in allografts on POD7. The mRNA level of IL-1β and IFN-γ of allografts was downregulated. Mechanistically, Ori-treated BMDCs suppressed T-cell proliferation and IFN-γ+CD4+ T-cell differentiation, along with the expansion of Tregs and IL-10+CD4+ T cells. Ori inhibited NOD, LRR-, and pyrin domain-containing protein 3 (NLRP3) expression; attenuated NF-κB and IκBα phosphorylation in LPS-activated BMDCs; downregulated NLRP3, Caspase-1, IL-1β, IL-18, and IFN-γ; and upregulated IL-10 expression.ConclusionsOur findings highlight the potential of Ori as a novel and natural IS agent to improve transplant tolerance. Ori could exert IS activity through decreasing IL-1β and IL-18 production and Th1 differentiation and proliferation and expanding Tregs via inhibiting the NF-κB/NLRP3 signaling pathway.


Author(s):  
O. M. Tsiroulnikova ◽  
I. V. Zhilkin ◽  
D. G. Akhaladze

Liver transplantation is a life-saving procedure for many forms of end-stage liver disease in pediatrics. Cytomegalovirus (CMV) is the most common and signifi cant posttransplant infection after pediatric liver transplant (PLT) with developing an episode of CMV infection or disease. It is well known that CMV increases risk of graft loss. The review presents aspects of etiology and epidemiology of CMV after PLT, approaches employed in diagnostics and prophylaxis of CMV, algorithms for valganciclovir dosing and methods to prevent complications associated with CMV. The latest data on current prevention strategies in pediatric liver transplantation centers in the world are also presented.


2018 ◽  
Vol 25 (2) ◽  
pp. 43-52
Author(s):  
Jo Wray ◽  
Claire Orrells ◽  
Helen Latch ◽  
Michael Burch

Abstract. Heart transplantation is the treatment of choice for children with end-stage heart disease. Coronary artery vasculopathy is, however, a significant morbidity and leading cause of late graft loss, and hyperlipidemia a risk factor for its development. Improving diet in this population could have important benefits for patients. We wanted to understand what influences decisions about food intake in this patient group. Dietary intentions and behavior were examined using a questionnaire based on the Theory of Planned Behavior (TPB) with 67 children who had undergone heart transplantation at least 12 months previously. The TPB model was significant for both healthy and unhealthy dietary behaviors, explaining 55% and 38% of the variance, respectively. Ten percent of children reported not eating any fruit and/or vegetables in the previous week and only 29% reported eating fruit and/or vegetables every day. The Theory of Planned Behavior provides a framework for explaining some specific dietary behaviors related to individual food groups in children who have undergone heart transplantation. These preliminary data support using this approach to inform the development of interventions to improve fruit and vegetable consumption but the approach may be less useful for explaining and developing interventions to reduce the consumption of unhealthy foods.


2013 ◽  
Vol 12 (1) ◽  
pp. 85-91 ◽  
Author(s):  
Odilson Marcos Silvestre ◽  
Fernando Bacal ◽  
Danusa de Souza Ramos ◽  
Jose L. Andrade ◽  
Meive Furtado ◽  
...  

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 2715
Author(s):  
Rodica Ana Ungur ◽  
Viorela Mihaela Ciortea ◽  
Laszlo Irsay ◽  
Alina Deniza Ciubean ◽  
Bogdana Adriana Năsui ◽  
...  

The non-steroidal anti-inflammatory drugs (NSAIDs) are the most used drugs in knee OA (osteoarthritis) treatment. Despite their efficiency in pain and inflammation alleviation, NSAIDs accumulate in the environment as chemical pollutants and have numerous genetic, morphologic, and functional negative effects on plants and animals. Ultrasound (US) therapy can improve pain, inflammation, and function in knee OA, without impact on environment, and with supplementary metabolic beneficial effects on cartilage compared to NSAIDs. These features recommend US therapy as alternative for NSAIDs use in knee OA treatment.


2021 ◽  
Vol 8 (4) ◽  
pp. 39
Author(s):  
Luciana Da Silveira Cavalcante ◽  
Shannon N. Tessier

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.


Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.


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