Lymph Angiogenesis After Lung Transplantation and Relation to Acute Organ Rejection in Humans
Lymph Angiogenesis After Lung Transplantation and Relation to Acute Organ Rejection in Humans
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DOI：
10.1016/j.athoracsur.2010.03.013
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发表时间：
2010-08-01
影响因子：
4.6
通讯作者：
Geissler, Hans Joachim
中科院分区：
文献类型：
--
作者：
Dashkevich, Alexey;Heilmann, Claudia;Geissler, Hans Joachim
背景。发现肾移植后的急性排斥反应与受体衍生的淋巴血管生成增加有关。然而，淋巴血管生成与肺移植急性排斥反应的关系尚不清楚。研究了23例肺移植受者（47例+/- 15岁，15例男性，19例双肺，4例单肺）在移植后14天和90天的支气管活检。对PROX-1（淋巴内皮标志物）和血管内皮生长因子受体（VEGFR） 1和2（毛细血管标志物）进行免疫组织染色。无排斥反应迹象的活检（国际心肺移植学会[ISHLT]分级A0， n = 27）与排斥反应分级A1/A2的活检（n = 19）进行比较。在移植后14天（p < 0.001）和90天（p < 0.001），以及在集体比较中（所有ISHLT分级为A1或A2的活检与所有分级为A0的活检相比，p < 0.001），排斥等级为A1或A2的活检显示PROX-1标记淋巴的密度显著高于A0级的活检。对于VEGFR-1和VEGFR-2，无论是在14天或90天，还是在集体比较中，都没有发现ISHLT A1或A2级与A0级之间的差异。肺移植后淋巴血管生成增加，PROX-1淋巴内皮标记物密度增加，与组织学上明显的急性器官排斥反应有关。虽然淋巴血管生成在急性器官排斥反应中的确切作用仍有待确定，但微血管和急性排斥反应之间的相互作用的进一步研究似乎是有必要的。在进一步的研究中，PROX-1浓度分析可能会发展成为一种新的排斥监测工具，补充传统的排斥分级。（Ann Thorac surgery 2010;90:406-12） (C) 2010年由胸外科学会出版
Background. Acute rejection after kidney transplantation was found to be associated with increased recipient-derived lymph angiogenesis. However, the relation of lymph angiogenesis to acute rejection in lung transplantation has not yet been investigated.Methods. Transbronchial biopsies from 23 lung transplant recipients (47 +/- 15 years old, 15 male, 19 double lungs, 4 single lungs), taken at 14 and 90 days after transplantation were investigated. Immunohistostaining for PROX-1 (an lymphatic endothelial marker) and for vascular endothelial growth factor receptor (VEGFR) 1 and 2 (blood capillary markers) was performed. Biopsies with no sign of rejection (International Society for Heart and Lung Transplantation [ISHLT] grade A0, n = 27) were compared with biopsies with rejection grade A1/A2 (n = 19).Results. Biopsies with ISHLT rejection grade A1 or A2 showed a significantly higher density of PROX-1 marked lymphatics in comparison with biopsies of grade A0 at 14 days (p < 0.001) and at 90 days (p < 0.001) after trans-plantation, and in the collective comparison (all biopsies with ISHLT grade A1 or A2 versus all biopsies with grade A0, p < 0.001). For VEGFR-1 and VEGFR-2, no difference was found between ISHLT grade A1 or A2 compared with grade A0, neither at 14 or 90 days nor in the collective comparison.Conclusions. Increased lymphatic angiogenesis after lung transplantation, demonstrated by increased density of the PROX-1 lymphatic endothelial marker, was associated with histologically evident acute organ rejection in humans. Although the exact role of lymphatic angiogenesis in acute organ rejection remains to be determined, further study of the interaction between the microvasculature and acute rejection seems warranted. Pending further investigation, analysis of PROX-1 density may develop into a new tool for rejection monitoring, supplementing conventional rejection grading. (Ann Thorac Surg 2010;90:406-12) (C) 2010 by The Society of Thoracic Surgeons