Innate immunity and cardiac allograft rejection.

MGH Transplant Center and Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Kidney international. Supplement 12/2010; DOI: 10.1038/ki.2010.417
Source: PubMed

ABSTRACT The development of immunosuppressive drugs to control adaptive immune responses has led to the success of heart transplantation as a therapy for end-stage heart failure. However, these agents are largely ineffective in suppressing components of the innate immune system. This distinction has gained clinical significance as mounting evidence now indicates that innate immune responses have important roles in the acute and chronic rejection of cardiac allografts including cardiac allograft vasculopathy (CAV). Whereas clinical interest in natural killer (NK) cells was once largely confined to the field of bone marrow transplantation, recent findings suggest that these cells can also participate in the acute rejection of cardiac allografts and in the development of CAV. Stimulation of Toll-like receptors (TLRs), another important component of innate immunity, by endogenous ligands released in response to ischemia/reperfusion is now known to cause an inflammatory milieu favorable to graft rejection. Finally, new data indicate that activation of complement is linked to acute rejection and CAV. In summary, the conventional wisdom that the innate immune system is of little importance in whole-organ transplantation is no longer tenable. The addition of strategies that target TLRs, NK cells, and complement will be necessary to prevent CAV completely and to eventually achieve long-term tolerance to cardiac allografts.

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    ABSTRACT: Ischemia reperfusion (IR) injury is a major issue in cardiac transplantation and inflammatory processes play a major role in myocardial IR injury. Long pentraxin-3 (PTX3) is a member of a phylogenetically conserved group of acute phase reactants that are involved in inflammation and innate immunity. In our study, hearts of C57BL/6 mice were flushed and stored in cold Bretschneider solution for 8 hours and then transplanted into syngeneic recipient. We found that both mRNA and protein levels of PTX3 were increased following myocardial IR injury; neutralizing antibody against PTX3 aggravated cardiomyocyte apoptosis and recruitment of neutrophils and macrophages. Troponin T (TnT) production on 24h after myocardial IR injury was reduced by exogenous PTX3 administration and increased by PTX3 neutralization in comparison with control. Cardiac output at 60 mmHg of afterload pressure was also increased in hearts with exogenous PTX3 administration and decreased with PTX3 neutralization (PTX3: 58.4 ± 7.4 ml/min; Control: 24.5 ± 3.8 ml/min; Anti- PTX3: 11.6 ± 1.7 ml/min; P<0.05). Furthermore, PTX3 restricted expansion of γδ T cell that was the major source of IL-17A and down-regulated expression of IL-23 and IL-17A. In conclusion, PTX3 played a protective role in cardiomyocyte IR injury. PTX3 ameliorated cardiomyocyte apoptosis and infiltration of neutrophil and macrophage and then improved hemodynamic performance. This was associated with restricted γδ T cell expansion and decreased IL-23/IL-17A expression. This article is protected by copyright. All rights reserved.
    Transplant International 09/2013; · 3.16 Impact Factor
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    ABSTRACT: Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies.
    Journal of Medical Radiation Sciences. 07/2014;
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    ABSTRACT: Cardiovascular disease remains the leading cause of mortality and morbidity worldwide so research continues into underlying mechanisms. Since innate immunity and its potent component mannan-binding lectin have been proven to play an important role in the inflammatory response during infection and ischaemia-reperfusion injury, attention has been paid to its role in the development of cardiovascular complications as well. This review provides a general outline of the structure and genetic polymorphism of MBL and its role in inflammation/tissue injury with emphasis on associations with cardiovascular disease. MBL appears to be involved in the pathogenesis of atherosclerosis and, in consequence, coronary artery disease and also inflammation and tissue injury after myocardial infarction and heart transplantation. The relationship between MBL and disease is rather complex and depends on different genetic and environmental factors. That could be why the data obtained from animal and clinical studies are sometimes contradictory proving not for the first time that innate immunity is a "double-edge sword," sometimes beneficial and, at other times disastrous for the host.
    BioMed Research International 01/2014; 2014:616817. · 2.71 Impact Factor


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