Shi Ruili, Yang Junbao, Jaramillo Andrés, Steward Nancy S, Aloush Aviva, Trulock Elbert P, Alexander Patterson G, Suthanthiran Manikkam, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110, USA.
Transpl Immunol. 2004 Jan;12(2):103-8. doi: 10.1016/j.trim.2003.11.002.
The levels of interleukin (IL)-15 and granzyme B mRNA expression have been correlated with acute rejection episodes of kidney and heart allografts. Thus, the purpose of this study was to determine whether a correlation exists between the expression of IL-15 and granzyme B and acute lung allograft rejection. Toward this, the levels of IL-15 and granzyme B mRNA expression were determined in bronchoalveolar lavage-derived alveolar macrophages and total cells, respectively, from lung transplant patients with stable lung allograft function and patients undergoing acute rejection episodes. The expression levels of IL-15 mRNA was significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (P=0.02). The expression levels of granzyme B mRNA was also significantly higher in the patients undergoing acute rejection as compared to patients with stable lung function (P=0.005). The Receiver-Operating-Characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 94% and specificity of 67% with the use of a cutoff value of 3.1 fg of granzyme B mRNA per microgram of total RNA (or 71% sensitivity and 75% specificity of a cutoff value of 9.1 fg/microg). These data indicate that IL-15 secreted by activated alveolar macrophages and granzyme B secreted by activated CD8+ cytotoxic T lymphocytes play important roles in the process of acute lung allograft rejection.
白细胞介素(IL)-15和颗粒酶B的mRNA表达水平已与肾和心脏同种异体移植的急性排斥反应相关。因此,本研究的目的是确定IL-15和颗粒酶B的表达与急性肺同种异体移植排斥反应之间是否存在相关性。为此,分别在肺移植功能稳定的患者和发生急性排斥反应的患者的支气管肺泡灌洗来源的肺泡巨噬细胞和总细胞中测定了IL-15和颗粒酶B的mRNA表达水平。与肺功能稳定的患者相比,发生急性排斥反应的患者中IL-15 mRNA的表达水平显著更高(P=0.02)。与肺功能稳定的患者相比,发生急性排斥反应的患者中颗粒酶B mRNA的表达水平也显著更高(P=0.005)。受试者工作特征曲线表明,使用每微克总RNA中颗粒酶B mRNA的截断值为3.1 fg时,预测急性排斥反应的敏感性为94%,特异性为67%(或截断值为9.1 fg/μg时,敏感性为71%,特异性为75%)。这些数据表明,活化的肺泡巨噬细胞分泌的IL-15和活化的CD8+细胞毒性T淋巴细胞分泌的颗粒酶B在急性肺同种异体移植排斥反应过程中起重要作用。