Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction.
Anti-type V collagen humoral immunity in lung transplant primary graft dysfunction.
复制标题
DOI：
10.4049/jimmunol.181.8.5738
复制
发表时间：
2008-10-15
期刊：
影响因子：
--
通讯作者：
Wilkes DS
中科院分区：
文献类型：
--
作者：
Iwata T;Philipovskiy A;Fisher AJ;Presson RG Jr;Chiyo M;Lee J;Mickler E;Smith GN;Petrache I;Brand DB;Burlingham WJ;Gopalakrishnan B;Greenspan DS;Christie JD;Wilkes DS
原发性移植物功能障碍（PGD）是肺移植后的主要并发症。我们报道抗 V 型胶原 (col(V)) T 细胞免疫与 PGD 密切相关。然而，预制抗 col(V) Ab 的作用及其在 PGD 中的潜在靶点尚不清楚。将 Col(V) 免疫血清、来自 col(V) 免疫大鼠的纯化 IgG 或 B 细胞转移至 WKY 大鼠肺同种移植受者中，然后评估肺病理学、细胞因子和 PaO2/FiO2（PGD 中肺功能障碍的指标）。移植后 4 天内，免疫血清、纯化的 IgG 和 B 细胞均诱导出与 PGD 一致的病理学；局部上调 IFN-γ、TNF-α 和 IL-1β；并导致 PaO2/FiO2 显着降低。转移前耗尽抗 col(V) Abs 表明 IgG2c 是介导损伤的主要亚型。共聚焦显微镜显示肺上皮细胞上有强烈的顶端col（V）表达，但内皮细胞上没有表达；这与 col(V) 免疫血清仅在上皮细胞中诱导补体依赖性细胞毒性的能力一致。对接受或未接受 PGD 的患者血浆进行的检查显示，较高水平的预制抗 col(V) 抗体与 PGD 的发生密切相关。这项研究证明了抗 col(V) 体液免疫在 PGD 中的重要作用，并将气道上皮确定为 PGD 的目标。
Primary graft dysfunction (PGD) is a major complication following lung transplantation. We reported that anti-type V collagen (col(V)) T cell immunity was strongly associated with PGD. However, the role of preformed anti-col(V) Abs and their potential target in PGD are unknown. Col(V) immune serum, purified IgG or B cells from col(V) immune rats were transferred to WKY rat lung isograft recipients followed by assessments of lung pathology, cytokines, and PaO2/FiO2, an index of lung dysfunction in PGD. Immune serum, purified IgG, and B cells all induced pathology consistent with PGD within 4 days posttransfer; up-regulated IFN-γ, TNF-α, and IL-1β locally; and induced significant reductions in PaO2/FiO2. Depleting anti-col(V) Abs before transfer demonstrated that IgG2c was a major subtype mediating injury. Confocal microscopy revealed strong apical col(V) expression on lung epithelial, but not endothelial cells; which was consistent with the ability of col(V) immune serum to induce complement-dependent cytotoxicity only in the epithelial cells. Examination of plasma from patients with or without PGD revealed that higher levels of preformed anti-col(V) Abs were strongly associated with PGD development. This study demonstrates a major role for anti-col(V) humoral immunity in PGD, and identifies the airway epithelium as a target in PGD.
登录
查看更多内容
影响因子：
4.4
作者：
Goers, Trudie A.;Ramachandran, Sabarinathan;Mohanakumar, Thalachallour
通讯作者：
Mohanakumar, Thalachallour
DOI：
10.1164/rccm.200409-1243oc
发表时间：
2005-06-01
影响因子：
24.7
作者：
Christie, JD;Kotloff, RM;Kimmel, SE
通讯作者：
Kimmel, SE
DOI：
10.1016/j.jtcvs.2005.08.039
发表时间：
2006-01-01
影响因子：
6
作者：
Whitson, BA;Nath, DS;Dahlberg, PS
通讯作者：
Dahlberg, PS
影响因子：
4.4
作者：
Nakashima, S;Qian, ZP;Baldwin, WM
通讯作者：
Baldwin, WM
影响因子：
9.6
作者：
Thabut, G;Vinatier, I;Mal, H
通讯作者：
Mal, H