Characterization of transfusion-elicited acute antibody-mediated rejection in a rat model of kidney transplantation.
Characterization of transfusion-elicited acute antibody-mediated rejection in a rat model of kidney transplantation.
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DOI：
10.1111/ajt.12674
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发表时间：
2014-05
期刊：
影响因子：
--
通讯作者：
Djamali A
中科院分区：
文献类型：
--
作者：
Huang G;Wilson NA;Reese SR;Jacobson LM;Zhong W;Djamali A
抗体介导的排斥反应（ABMR）的动物模型可以提供支持概念验证的重要证据。我们通过在肾移植前3周将供体血液（Brown Norway RT 1 n）输注到完全错配的受体（刘易斯RT 1 l）中来引发供体特异性抗体（DSA）。致敏受者在移植后1周抗供体脾细胞IgG 1、IgG 2b和IgG 2c DSA升高。组织学与ABMR一致，其特征在于弥漫性管周毛细血管C4d和中度微血管炎症伴管周毛细血管炎+肾小球炎> 2。肾同种异体移植组织的免疫荧光研究表明，致敏动物中的CD 68/CD 3比值更大，主要是M1（促炎）表型，与细胞因子基因分析一致，表明主要是T辅助细胞（TH）1（干扰素-γ，IL-2）特征。免疫印迹分析证实了M1巨噬细胞表型的激活，因为干扰素调节因子5、诱导型一氧化氮合酶和吞噬细胞NADPH氧化酶2显著上调。急性ABMR致敏患者的临床活检样本证实了人类M1巨噬细胞表型的优势。尽管没有小管炎，我们不能排除T细胞介导的排斥反应的影响。这些研究表明，M1巨噬细胞和TH 1细胞因子在致敏同种异体移植受者急性混合性排斥反应的发病机制中起重要作用。
Animal models of antibody-mediated rejection (ABMR) may provide important evidence supporting proof of concept. We elicited donor-specific antibodies (DSA) by transfusion of donor blood (Brown Norway RT1n) into a complete mismatch recipient (Lewis RT1l) 3 weeks prior to kidney transplantation. Sensitized recipients had increased anti-donor splenocyte IgG1, IgG2b and IgG2c DSA 1 week after transplantation. Histopathology was consistent with ABMR characterized by diffuse peritubular capillary C4d and moderate microvascular inflammation with peritubular capillaritis + glomerulitis > 2. Immunofluorescence studies of kidney allograft tissue demonstrated a greater CD68/CD3 ratio in sensitized animals, primarily of the M1 (pro-inflammatory) phenotype, consistent with cytokine gene analyses that demonstrated a predominant T helper (TH)1 (interferon-γ, IL-2) profile. Immunoblot analyses confirmed the activation of the M1 macrophage phenotype as interferon regulatory factor 5, inducible nitric oxide synthase and phagocytic NADPH oxidase 2 were significantly up-regulated. Clinical biopsy samples in sensitized patients with acute ABMR confirmed the dominance of M1 macrophage phenotype in humans. Despite the absence of tubulitis, we were unable to exclude the effects of T cell–mediated rejection. These studies suggest that M1 macrophages and TH1 cytokines play an important role in the pathogenesis of acute mixed rejection in sensitized allograft recipients.
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DOI：
10.1111/ajt.12589
发表时间：
2014-02
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Djamali A;Kaufman DB;Ellis TM;Zhong W;Matas A;Samaniego M
通讯作者：
Samaniego M
DOI：
10.1111/j.1600-6143.2012.04081.x
发表时间：
2012-08
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Djamali A;Reese S;Hafez O;Vidyasagar A;Jacobson L;Swain W;Kolehmainen C;Huang L;Wilson NA;Torrealba JR
通讯作者：
Torrealba JR
影响因子：
2.7
作者：
Akiyoshi, Takurin;Hirohashi, Tsutomu;Alessandrini, Alessandro;Chase, Catherine M.;Farkash, Evan A.;Smith, R. Neal;Madsen, Joren C.;Russell, Paul S.;Colvin, Robert B.
通讯作者：
Colvin, Robert B.
DOI：
10.1111/j.1600-6143.2008.02463.x
发表时间：
2009-01
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Djamali A;Vidyasagar A;Adulla M;Hullett D;Reese S
通讯作者：
Reese S
DOI：
10.1111/j.1600-6143.2012.04073.x
发表时间：
2012-08
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Hattori Y;Bucy RP;Kubota Y;Baldwin WM 3rd;Fairchild RL
通讯作者：
Fairchild RL