Inhibition of chronic rejection by antibody induced vascular accommodation in fully allogeneic heart allografts
Inhibition of chronic rejection by antibody induced vascular accommodation in fully allogeneic heart allografts
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DOI：
10.1097/01.tp.0000188952.10692.18
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发表时间：
2005-12-15
期刊：
影响因子：
6.2
通讯作者：
Ghobrial, RM
中科院分区：
文献类型：
--
作者：
Semiletova, NV;Shen, XD;Ghobrial, RM
背景在异种免疫反应中，抗体反应的改变作为一种效应保护机制诱导移植物调节的潜在作用已被广泛研究。在这里，我们研究了在完全不匹配的同种异体心脏移植模型中，与血管内皮结合的抗体的保护作用。WF心脏移植物的ACI受体用同种异体嵌合[α（1h）（l/u））-RT1.A（a）I类主要组织相容性复合体（MHC）提取物（1 mg/大鼠，p. v.第0天）或高剂量CsA（10 mg/kg/天，p.o.，第0-6天）。在移植后100天通过免疫组织学评估心脏移植物的慢性排斥反应和/或血管调节的证据。凋亡或抗凋亡机制的激活通过DNA片段化（TUNEL）分析来验证。同种异体嵌合体治疗可抑制ACI患者的慢性排斥反应，无新生内膜形成，并诱导完全同种异体WF心脏的血管调节。这种调节通过IgG和IgM血管内皮结合以及DNA片段化的显着减少而明显。相比之下，CsA治疗导致明显的新生内膜增生，没有血管调节的证据。免疫组织化学分析未能证明血管内皮抗体结合。CsA治疗后出现严重的慢性排斥反应，并伴有明显的DNA断裂。异基因移植中体液免疫的改变诱导血管调节。血管调节是异基因嵌合体MHC I类分子治疗后抑制移植物血管病变的潜在机制。
Background. The potential role of altered antibody responses as an effector protective mechanism to induce graft accommodation has been widely investigated in xenogeneic responses. Here we investigate the protective effects of antibody binding to vascular endothelium in a fully mismatched allogeneic model of heart transplantation.Methods. ACI recipients of WF cardiac grafts were treated either with allochimeric [alpha(1h) (l/u))-RT1.A(a) class I major histocompatibility complex (MHC) extracts (I mg/rat, p.v. day 0) or high dose of CsA (10 mg/kg/day, p.o., day 0-6). Cardiac allografts were evaluated at 100 days posttransplant by immunohistology for evidence of chronic rejection and/or vascular accommodation. Activation of apoptotic or antiapoptotic mechanisms was verified by DNA fragmentation (TUNEL) analysis.Results. Allochimeric therapy resulted in inhibition of chronic rejection, absence of neointimal formation and induction of vascular accommodation of fully allogeneic WF hearts in ACI hosts. Such accommodation was evident by IgG and IgM vascular endothelial binding and marked reduction of DNA fragmentation. In contrast, CsA therapy resulted in marked neointimal proliferation, without evidence of vascular accommodation. Immunohistochemical analysis failed to demonstrate vascular endothelial antibody binding. Further, severe chronic rejection following CsA treatment was accompanied by marked DNA fragmentation.Conclusion. Alteration of humoral immunity induces vascular accommodation in allogeneic transplantation. Vascular accommodation is the underlying mechanism for inhibition allograft vasculopathy following allochimeric MHC class I therapy.