Turunen J P, Paavonen T, Majuri M L, Tiisala S, Mattila P, Mennander A, Gahmberg C G, Häyry P, Tamatani T, Miyasaka M
Department of Bacteriology and Immunology, University of Helsinki, Finland.
Eur J Immunol. 1994 May;24(5):1130-6. doi: 10.1002/eji.1830240518.
Kidney allograft rejection is an inflammatory process dominated by lymphocytes. During rejection lymphocytes preferentially adhere to the peritubular capillary endothelium (PTCE), which acquires morphological features common to high endothelium. These observations indicate that PTCE is the site of lymphocyte entry into the rejecting renal allograft. Of the identified endothelial adhesion molecules, ICAM-1 was already expressed on the endothelium of normal kidneys, and its expression was strongly enhanced during rejection without site-specific restriction. VCAM-1 was not expressed on the endothelium of normal or syngeneic kidneys, but its expression was induced during allograft rejection not only in PTCE, but occasionally also on the endothelium of larger vessels. Sialyl Lewisx (sLex) showed a very restricted pattern of expression; endothelium was sLex-negative both in control and syngeneic kidneys. On the other hand, PTCE reacted strongly with anti-sLex antibody in allografts. When kidney frozen sections were treated with sialidase the binding of lymphocytes decreased by 70%. Low-dose chymotrypsin treatment of lymphocytes, known to remove L-selectin from the lymphocyte surface, decreased their binding to PTCE by 60%. Likewise lymphocyte adhesion to PTCE was inhibited by 70% by anti-sLex- and anti-L-selectin-antibodies and by sLex tetrasaccharide. Finally PTCE in the allografts, but not in syngeneic grafts or normal kidneys, bound an L-selectin-IgG fusion protein, indicating that ligands for L-selectin were induced during rejection.
肾移植排斥反应是一个以淋巴细胞为主导的炎症过程。在排斥反应期间，淋巴细胞优先黏附于肾小管周围毛细血管内皮（PTCE），后者呈现出高内皮细胞共有的形态学特征。这些观察结果表明，PTCE是淋巴细胞进入正在发生排斥反应的肾移植器官的部位。在已确定的内皮黏附分子中，ICAM-1在正常肾脏的内皮细胞上已经表达，并且其表达在排斥反应期间强烈增强，且无位点特异性限制。VCAM-1在正常或同基因肾脏的内皮细胞上不表达，但在同种异体移植排斥反应期间，其表达不仅在PTCE中被诱导，偶尔也在较大血管的内皮细胞上被诱导。唾液酸化路易斯x（sLex）呈现出非常有限的表达模式；在对照和同基因肾脏中，内皮细胞均为sLex阴性。另一方面，在同种异体移植中，PTCE与抗sLex抗体发生强烈反应。当肾冰冻切片用唾液酸酶处理时，淋巴细胞的黏附减少了70%。已知低剂量胰凝乳蛋白酶处理淋巴细胞可从淋巴细胞表面去除L-选择素，这使其与PTCE的黏附减少了60%。同样，抗sLex和抗L-选择素抗体以及sLex四糖可使淋巴细胞与PTCE的黏附受到70%的抑制。最后，同种异体移植中的PTCE（而非同基因移植或正常肾脏中的PTCE）结合了一种L-选择素-IgG融合蛋白，这表明在排斥反应期间诱导产生了L-选择素的配体。
