Alpha-1-antitrypsin in cell and organ transplantation.
Alpha-1-antitrypsin in cell and organ transplantation.
复制标题
DOI：
10.1111/ajt.14756
复制
发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Koulmanda M
中科院分区：
文献类型：
--
作者：
Berger M;Liu M;Uknis ME;Koulmanda M
供体器官的有限可用性和缺血再灌注损伤（IRI）的风险严重限制了器官移植。可以预防或减少IRI的治疗方法可能会通过增加边缘器官的使用和减少丢弃来增加移植数量。α-1抗胰蛋白酶（AAT）是一种急性期反应物和丝氨酸蛋白酶抑制剂，可限制炎症组织损伤。纯化血浆来源的AAT在30多年的使用中具有良好的耐受性，可预防AAT缺陷个体的肺气肿。越来越多的证据表明，AAT具有额外的抗炎和组织保护作用，包括改善线粒体膜稳定性、抑制细胞凋亡、抑制核因子κ B活化、调节促炎细胞因子与抗炎细胞因子平衡以及促进免疫耐受。细胞培养和动物研究表明，AAT限制组织损伤并促进细胞和组织存活。AAT可以通过下调早期炎症和促进调节性T细胞的诱导和稳定来促进动物模型中的耐受性。AAT的多种细胞内和免疫调节作用及其在患者中的良好耐受性表明它可能在移植中有用。计划和/或正在进行的临床试验应有助于确定动物和细胞研究的承诺是否会通过改善人体器官移植的结果来实现。虽然传统上被认为是丝氨酸蛋白酶的细胞外抑制剂，但α-1-抗胰蛋白酶也具有细胞内效应，可能对移植有益，包括抑制细胞凋亡和NF-κ B活化，调节促炎细胞因子与抗炎细胞因子的平衡，并促进耐受。
Limited availability of donor organs and risk of ischemia‐reperfusion injury (IRI) seriously restrict organ transplantation. Therapeutics that can prevent or reduce IRI could potentially increase the number of transplants by increasing use of borderline organs and decreasing discards. Alpha‐1 antitrypsin (AAT) is an acute phase reactant and serine protease inhibitor that limits inflammatory tissue damage. Purified plasma–derived AAT has been well tolerated in more than 30 years of use to prevent emphysema in AAT‐deficient individuals. Accumulating evidence suggests that AAT has additional anti‐inflammatory and tissue‐protective effects including improving mitochondrial membrane stability, inhibiting apoptosis, inhibiting nuclear factor kappa B activation, modulating pro‐ vs anti‐inflammatory cytokine balance, and promoting immunologic tolerance. Cell culture and animal studies have shown that AAT limits tissue injury and promotes cell and tissue survival. AAT can promote tolerance in animal models by downregulating early inflammation and favoring induction and stabilization of regulatory T cells. The diverse intracellular and immune‐modulatory effects of AAT and its well‐established tolerability in patients suggest that it might be useful in transplantation. Clinical trials, planned and/or in progress, should help determine whether the promise of the animal and cellular studies will be fulfilled by improving outcomes in human organ transplantation. Although traditionally considered an extracellular inhibitor of serine proteases, alpha‐1‐antitrypsin also has intracellular effects that may be beneficial in transplantation, including inhibiting apoptosis and NF‐kB activation, modulating proversus anti‐inflammatory cytokine balance, and promoting tolerance.
登录
查看更多内容
DOI：
10.4049/jimmunol.1500740
发表时间：
2015-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Frenzel E;Wrenger S;Brügger B;Salipalli S;Immenschuh S;Aggarwal N;Lichtinghagen R;Mahadeva R;Marcondes AM;Dinarello CA;Welte T;Janciauskiene S
通讯作者：
Janciauskiene S
影响因子：
20.3
作者：
Marcondes, A. Mario;Karoopongse, Ekapun;Deeg, H. Joachim
通讯作者：
Deeg, H. Joachim
影响因子：
8.9
作者：
Iskender, Ilker;Sakamoto, Jin;Liu, Mingyao
通讯作者：
Liu, Mingyao
影响因子：
24.1
作者：
Abecassis, Avishag;Schuster, Ronen;Lewis, Eli C.
通讯作者：
Lewis, Eli C.
影响因子：
37.8
作者：
Daemen, MARC;Heemskerk, VH;Buurman, WA
通讯作者：
Buurman, WA