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实验性肺移植的急性排斥反应:血管内单核白细胞的特征

Acute rejection of experimental lung allografts: characterization of intravascular mononuclear leukocytes.

作者信息

Blöcher Sonja, Wilker Sigrid, Sucke Jochen, Pfeil Uwe, Dietrich Hartmut, Weimer Rolf, Steger Klaus, Kaufmann Andreas, Hirschburger Markus, Plötz Christian, Padberg Winfried, Grau Veronika

机构信息

Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, University of Giessen Lung Center, Giessen, Germany.

出版信息

Clin Immunol. 2007 Jul;124(1):98-108. doi: 10.1016/j.clim.2007.04.005. Epub 2007 May 21.

Abstract

Leukocytes interacting with endothelia of lung allografts probably play a seminal role in acute rejection, but have not been characterized before. Transplantation was performed in the Lewis to Lewis and in the Dark Agouti to Lewis rat strain combinations. DNA replication was detected in T-cells on day 2 after pulse-labelling in vivo with 5-bromo-2'-deoxyuridine (BrdU). On day 5, leukocytes were isolated by intensive perfusion the graft, subject to flow cytometry and to quantitative RT-PCR. About 34 million leukocytes accumulated in allograft vessels, but only 10 and 6 million cells in isografts and control lungs, respectively. During rejection, IFN-gamma, IL-1beta and IL-10 mRNA expression increased, IL-12 mRNA decreased, whereas IL-2, IL-6, TNF-alpha, and TGF-beta mRNA did not change. The phenotype of graft monocytes was partially activated and intravascular T-cells proliferated. In conclusion, during rejection, monocytes with unusual properties accumulate and T-lymphocytes are activated in lung allograft blood vessels.

摘要

与肺移植内皮相互作用的白细胞可能在急性排斥反应中起关键作用,但此前尚未被明确。在Lewis到Lewis以及Dark Agouti到Lewis大鼠品系组合中进行了移植。在用5-溴-2'-脱氧尿苷(BrdU)进行体内脉冲标记后第2天,在T细胞中检测到DNA复制。在第5天,通过对移植物进行强化灌注分离白细胞,进行流式细胞术和定量逆转录聚合酶链反应(RT-PCR)。同种异体移植血管中积聚了约3400万个白细胞,但同基因移植和对照肺中分别只有1000万和600万个细胞。在排斥反应期间,γ干扰素(IFN-γ)、白细胞介素-1β(IL-1β)和白细胞介素-10(IL-10)的信使核糖核酸(mRNA)表达增加,IL-12的mRNA减少,而IL-2、IL-6、肿瘤坏死因子-α(TNF-α)和转化生长因子-β(TGF-β)的mRNA没有变化。移植物单核细胞的表型部分被激活,血管内T细胞增殖。总之,在排斥反应期间,具有异常特性的单核细胞积聚,肺同种异体移植血管中的T淋巴细胞被激活。

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