Increased levels of T cell granzyme b in bronchiolitis obliterans syndrome are not suppressed adequately by current immunosuppressive regimens
Increased levels of T cell granzyme b in bronchiolitis obliterans syndrome are not suppressed adequately by current immunosuppressive regimens
复制标题
目前的免疫抑制方案未能充分抑制闭塞性细支气管炎综合征中 T 细胞颗粒酶 b 水平的升高
DOI：
10.1111/j.1365-2249.2009.04008.x
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发表时间：
2009
影响因子：
4.6
通讯作者：
M. Holmes
中科院分区：
文献类型：
--
作者：
S. Hodge;G. Hodge;J. Ahern;C. Liew;Peter Hopkins;Daniel C. Chambers;P. Reynolds;M. Holmes
Bronchiolitis obliterans syndrome (BOS) is characterized by persistent alloreactive, infective and non‐specific epithelial injury, loss of epithelial integrity and dysregulated repair. We have reported increased apoptosis of epithelial cells collected from the large airway in lung transplant recipients. As part of the alloreactive response, T cells induce apoptosis of target epithelial cells by secreting granzyme b. We hypothesized that granzyme b would be increased in lung transplant patients with acute rejection and BOS and that commonly used immunosuppressive agents would fail to suppress this serine protease adequately. We investigated intracellular T cell granzyme b in blood, bronchoalveolar lavage (BAL) and large airway brushing (23 controls, 29 stable transplant, 23 BOS, 28 acute rejection, 31 infection) using flow cytometry and assessed the effect of clinically relevant concentrations of cyclosporin A, tacrolimus, methylprednisolone and a protease inhibitor, gabexate mesilate, on in vitro granzyme b production. Granzyme b was increased significantly in all compartments of all transplant groups compared to controls. Surprisingly, granzyme b was even higher in patients with BOS than in patients with acute rejection. In longitudinal analysis in three patients, blood granzyme b increased prior to or at the onset of BOS. In vitro, methylprednisolone and gabexate mesilate had no effect and cyclosporin A and tacrolimus only a moderate effect on production of granzyme b by CD8+ T cells. Increased T cell granzyme b production may contribute to BOS pathogenesis and is not curtailed by current immunosuppressants. Longitudinal investigation of granzyme b in blood may provide an adjunctive non‐invasive method for predicting BOS/OB.
经支气管活检在肺移植受者管理中的作用。
DOI：
--
发表时间：
1993
期刊：
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
影响因子：
--
作者：
Sibley,RK;Berry,GJ;Tazelaar,HD;Kraemer,MR;Theodore,J;Marshall,SE;Billingham,ME;Starnes,VA
通讯作者：
Starnes,VA
人颗粒酶 B 降解软骨细胞合成的基质中的聚集蛋白聚糖蛋白多糖。
DOI：
--
发表时间：
1993
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Froelich,CJ;Zhang,X;Turbov,J;Hudig,D;Winkler,U;Hanna,WL
通讯作者：
Hanna,WL