Andrade Cristiano Feijó, Kaneda Hiroyuki, Der Sandy, Tsang Melanie, Lodyga Monika, Chimisso Dos Santos Claudia, Keshavjee Shaf, Liu Mingyao
Thoracic Surgery Research Laboratory, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2006 Nov;25(11):1317-23. doi: 10.1016/j.healun.2006.09.017.
Innate immunity is the first line of host defense against invading microorganisms, which is mediated by specific pathogen recognition molecules called toll-like receptors (TLRs). TLRs can also recognize endogenous "danger" signals, resulting in cytokine production and activation of the adaptive immune system. We hypothesized that gene expression of TLRs during lung transplantation may be affected by the donor condition and the ischemia-reperfusion process, which may subsequently influence graft function.
Lung biopsies from 14 patients were collected before and after reperfusion, and mRNA levels of TLRs, cytokines (interleukin [IL]-1beta, IL-6, IL-8, IL-10 and interferon-gamma) and heat-shock protein 70 (HSP70) were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR).
In cold-preserved donor lungs, all TLRs (except TLR3) showed significant correlations with one another and also with the cytokines examined. Expression of several TLRs and cytokines correlated with the intubation time of donors. TLR4 gene expression correlated closely with IL-8 before and after reperfusion (p </= 0.01). After reperfusion, HSP70 mRNAs increased significantly (p < 0.05).
Differential expression levels of TLRs and cytokine genes likely reflect the inflammatory status of lung grafts; correlation of TLR genes with cytokine genes and clinical conditions implicates a potential role of TLRs in early graft responses.
固有免疫是宿主抵御入侵微生物的第一道防线，由称为Toll样受体（TLR）的特定病原体识别分子介导。TLR还可识别内源性“危险”信号，从而导致细胞因子产生并激活适应性免疫系统。我们推测，肺移植过程中TLR的基因表达可能受供体状况和缺血再灌注过程的影响，进而可能影响移植物功能。
收集14例患者再灌注前后的肺活检组织，采用定量实时逆转录-聚合酶链反应（RT-PCR）检测TLR、细胞因子（白细胞介素[IL]-1β、IL-6、IL-8、IL-10和干扰素-γ）及热休克蛋白70（HSP70）的mRNA水平。
在冷保存的供体肺中，所有TLR（除TLR3外）相互之间以及与所检测的细胞因子均显示出显著相关性。几种TLR和细胞因子的表达与供体的插管时间相关。再灌注前后，TLR4基因表达与IL-8密切相关（p≤0.01）。再灌注后，HSP70 mRNA显著增加（p<0.05）。
TLR和细胞因子基因的差异表达水平可能反映了肺移植物的炎症状态；TLR基因与细胞因子基因及临床状况的相关性表明TLR在移植物早期反应中可能发挥作用。
