Increased apoptosis is specific for acute rejection in rat small bowel transplant

Apoptosis has been associated with several events in solid organ transplantation, including ischemia/reperfusion (IR) injury and acute rejection. To determine whether apoptosis-profiles may distinguish these two conditions, we analyzed apoptosis rates in a rat orthotopic small bowel transplant (SBT) model. SBT was performed in Lewis rats with either freshly harvested or preserved (4 h, in UW at 4 degrees C) syngeneic and allogeneic (Brown-Norway) grafts. Bowel samples were collected 2 h after reperfusion and on small bowel transplant postoperative days (POD) 1, 4, and 7. Apoptosis was detected by measuring levels of histone-associated DNA fragments and caspase 3 expression, and by determining apoptotic body counts. All markers measured 2 h after reperfusion increased profoundly in association with preservation. After a significant decrease on POD 1, apoptosis rates rose again between POD 4 and 7 only in allogeneic grafts. This distinct second increase in apoptosis may be an early and specific sign of acute rejection.     

异体猪真皮在重组复合皮移植中的作用研究

目的 用胰酶消化法降低异体真皮的抗原性后,探讨不同类型的异体真皮与自体薄皮片重组后对猪复合皮成活质量的影响。方法 移植实验分三组,婴儿组为异体新生猪真皮+成年猪自体表皮皮片;成年组为异体成年猪真皮+成年猪自体表皮皮片;对照组为成年猪自体表皮皮片。术后观察三组皮片的成活质量及组织学变化。结果 根据皮片的成活率、收缩率、瘢痕增生和组织结构的完整性等情况进行综合分析,皮片质量的优劣依次是婴儿组,成年组,对照组。结论 低抗原性的异体真皮能改进重组复合皮移植的质量,而且以含异体新生儿猪真皮组成的复合皮效果最佳。     

Alloimmune Activation Enhances Innate Tissue Inflammation/Injury in a Mouse Model of Liver Ischemia/Reperfusion Injury

The deleterious sensitization to donor MHC Ags represents one of the most challenging problems in clinical organ transplantation. Although the role of effector/memory T cells in the rejection cascade has been extensively studied, it remains unknown whether and how these ‘Ag‐specific’ cells influence host innate immunity, such as tissue inflammation associated with ischemia and reperfusion injury (IRI). In this study, we analyzed how allogeneic skin transplant (Tx) affected the sequel of host's own liver damage induced by partial warm ischemia and reperfusion. Our data clearly showed that allo‐Tx recipients had increased inflammatory response against IR insult in their native livers, as evidenced by significantly more severe hepatocelluar damage, compared with syngeneic Tx recipient controls, and determined by serum ALT levels, liver histology (Suzuki's score) and intrahepatic proinflammatory gene inductions (TNF‐α, IL‐1β and CXCL10). The CD4 T cells, but neither CD8 nor NK cells, mediated the detrimental effect of allo‐Ag sensitization in liver IRI. Furthermore, CD154, but not IFN‐γ, was the key mechanism in allo‐Tx recipients to facilitate IR‐triggered liver damage. These results provide new evidence that alloreactive CD4 T cells are capable of enhancing innate tissue inflammation and organ injury via an Ag‐nonspecific CD154‐dependent but IFN‐γ independent mechanism.     

移植心脏血管病变的研究进展

本文从移植心脏[冠状动脉]血管病变(cardiac graft vasculopathy,CGV)的发病机制、诊断及治疗手段的角度出发,归纳总结了现阶段对其病理学、监测与诊治的理解与认识,为科学合理地预防、诊断、治疗CGV以改善心脏移植受者生存提供思路。     

Donor polymorphisms in Toll-like receptor-4 influence the development of rejection after renal transplantation

BACKGROUND: Although innate immunity is crucial to host defense against pathogens, the extent to which innate immune mechanisms participate in the rejection of allogenic tissues in humans is unknown. We hypothesize that activation of innate immunity through Toll-like receptors (TLRs) critically regulates the development of renal allograft rejection. We have recently demonstrated decreased acute rejection in lung transplant recipients heterozygous for either of two functional polymorphisms in TLR4 associated with endotoxin hyporesponsiveness. In the present investigation, we sought to evaluate the role of innate immune activation through TLR4, in either donor or recipient, upon the development of renal allograft rejection. METHODS: Patients and donors were screened for the TLR4 functional polymorphisms (Asp299Gly and Thr399Ile) by polymerase chain reaction (PCR) using sequence-specific primers. RESULTS: The incidence of biopsy-proven acute renal allograft rejection was significantly reduced in patients receiving donor grafts heterozygous for the Asp299Gly or Thr399Ile alleles, when compared with wild type (22% vs. 0%, respectively, p = 0.02). There was no association with recipient TLR4 allele and rejection. CONCLUSIONS: The results suggest activation of innate immunity through TLR4 in the donor kidney contributes to the development of acute rejection after renal transplantation.     

神经炎症在阿尔茨海默病中作用的研究进展

阿尔茨海默病（Alzheimer's disease, AD）是一种进行性发展的致死性神经退行性病变,是痴呆中最常见的类型。该病起病隐匿且病程持续时间长,但病因及发病机制目前尚未完全明确,现已有研究表明中枢神经系统炎症可能在其中发挥重要作用。文章就近年来神经炎症在AD中作用的最新研究进展进行综述,重点阐述小胶质细胞、星...     

神经炎症在阿尔茨海默病中作用的研究进展

阿尔茨海默病（Alzheimer's disease, AD）是一种进行性发展的致死性神经退行性病变,是痴呆中最常见的类型。该病起病隐匿且病程持续时间长,但病因及发病机制目前尚未完全明确,现已有研究表明中枢神经系统炎症可能在其中发挥重要作用。文章就近年来神经炎症在AD中作用的最新研究进展进行综述,重点阐述小胶质细胞、星形胶质细胞、神经元和适应性免疫在其中的具体机制,旨在为进一步探讨神经炎症在AD发生和发展过程中的作用提供新的理论依据。     

宿主对肺孢子菌免疫反应研究进展

肺孢子菌是一种机会感染性真菌,感染后可引起肺孢子菌肺炎(PCP),是获得性免疫缺陷综合征、器官移植术后以及肿瘤放化疗后等免疫功能低下或缺陷人群常见的并发症及死亡原因.随着免疫功能低下及缺陷人群例数的增加,PCP发病率也呈上升趋势.虽然免疫功能受损是PCP发病的基础,但既往研究表明,免疫介导的炎症反应同时也是导致PCP患...     

Preservation injury and acute rejection of rat intestinal grafts: Protection afforded by pyruvate

Pyruvate has been shown to prevent intestinal mucosal injury after ischemia-reperfusion. The aim of the present study was to determine whether pyruvate can (1) prevent postreperfusion mucosal injury occurring after intestinal preservation and subsequent transplantation and (2) exert a protective effect on the intestinal graft mucosa during acute rejection. Preservation mucosal injury was evaluated, after 2 hours of reperfusion, by comparing grafts transplanted in a rat syngeneic combination (ACI to ACI) after 2 hours of cold preservation using pyruvate (n = 6) or placebo (n = 6). Mucosal parameters obtained during acute rejection (allogeneic combination: ACI to Lewis) were compared between placebo-treated (n =6) and pyruvate-treated (n = 6) animals. Tissue injury was evaluated by histopathologic examination, oxygen free radical production by luminol-enhanced chemiluminescence, and degree of neutrophil infiltration by myeloperoxidase staining. After reperfusion of the preserved grafts and during acute rejection, mucosal oxygen free radical levels and the number of infiltrating neutrophils were significantly (P <0.05) increased in the untreated grafts, whereas there was a statistically significant inhibition of these parameters in those treated with pyruvate. Mucosal injury, seen after reperfusion of the preserved grafts, was prevented by pyruvate. The histopathologic abnormalities observed in the untreated grafts during rejection were also significantly reduced by pyruvate. Treatment with pyruvate before cold preservation of intestinal grafts, in this rat model, reduced reperfusion mucosal injury, neutrophil infiltration, and oxygen free radical production. Oxygen free radicals were produced in the mucosa of the graft during acute rejection and their production was reduced by pyruvate, which exerted a protective effect on the rejecting allograft mucosa.     

调节性T细胞在组织损伤修复中的作用及其调控机制研究进展

器官损伤后修复策略一直是再生医学领域研究的热点。传统的损伤修复方案多通过间充质干细胞及各种生长因子促进组织修复,但其受到安全性和经济性的制约,因此迫切需要寻找新的促进组织修复与再生的方法。目前已有较多研究证据显示,免疫系统在组织再生与修复中发挥着重要的作用。近年来,关于适应性免疫在组织修复中的研究日益增多,尤其是调节性T细胞,有资料提示其参与了多种脏器损伤修复与组织再生过程。本文概要介绍了调节性T细胞在不同脏器损伤中的修复效应及其调控机制新进展,旨在为未来设计出具有良好免疫调控性能的修复材料提供新思路。