Lemström K, Koskinen P, Häyry P
Transplantation Laboratory, University of Helsinki, Finland.
J Heart Lung Transplant. 1995 Mar-Apr;14(2):205-13.
Adhesion of leukocytes to vascular endothelium and their migration from the circulation into underlying tissue is regulated by an array of inducible cell adhesion molecules. We determined the kinetics and expression patterns of adhesion molecules expressed by the endothelia of rat cardiac allografts including the following: major histocompatibility complex class II (OX6), intercellular adhesion molecule-1 (1A29), vascular cell adhesion molecule-1 (5F10), leukocyte function-associated antigen-1 alpha-chain (WT.1), the common beta-chain of beta 2 integrins (WT.3), and very late activation antigen-4 (HP2.1) on inflammatory cells.
Intraabdominal heterotopic cardiac allografts (n = 12) were transplanted from the dark agouti (DA) rats (AG-B4, RT1a) to the Wistar-Furth (WF) rats (AG-B2, RT1v) strain and syngeneic controls (n = 12) were transplanted from dark agouti rat donors to dark agouti rat recipients. The grafts were removed 1, 3, and 5 days after transplantation, and cryostat sections were prepared for indirect immunoperoxidase staining with monoclonal antibodies. The intensity of adhesion molecule expression was scored from 0 to 3 in a blind review.
In nontransplanted dark agouti rat hearts, intercellular adhesion molecule-1 was constitutively expressed at a low level on capillary (0.5 +/- 0.5) and postcapillary venular (0.5 +/- 0.2) endothelia. In syngeneic controls, the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 was also faint and not induced, but a clear induction of class II expression was found on capillary endothelia. Large vessels stained negative for adhesion molecules. In allografts, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, but not class II, were significantly upregulated on capillary endothelia (p < 0.05). On postcapillary venular endothelia, a distinct induction (p < 0.05) of all three molecules was observed during acute rejection 5 days after transplantation. Concomitantly, the inflammatory leukocytes expressed high levels of leukocyte function-associated antigen-1 alpha-chain and beta-chain in the perivascular space. The expression of very late activation antigen-4 by lymphocytes was, however, nonexistent. In allograft arteries and arterioles, class II and vascular cell adhesion molecule-1, but not intercellular adhesion molecule-1, were weakly expressed during acute rejection.
Our results suggest that postcapillary venular endothelia may be the major site for leukocyte extravasation during acute cardiac allograft rejection in the rat model.
白细胞与血管内皮的黏附以及它们从循环系统迁移至下方组织的过程受一系列诱导性细胞黏附分子调控。我们测定了大鼠心脏同种异体移植物内皮表达的黏附分子的动力学和表达模式，包括以下分子：主要组织相容性复合体II类分子（OX6）、细胞间黏附分子-1（1A29）、血管细胞黏附分子-1（5F10）、白细胞功能相关抗原-1α链（WT.1）、β2整合素的共同β链（WT.3）以及炎症细胞上的极迟活化抗原-4（HP2.1）。
将腹腔异位心脏同种异体移植物（n = 12）从黑褐大鼠（DA大鼠，AG-B4，RT1a）移植至Wistar-Furth（WF）大鼠（AG-B2，RT1v），并将同基因对照（n = 12）从黑褐大鼠供体移植至黑褐大鼠受体。移植后1、3和5天取出移植物，制备冰冻切片，用单克隆抗体进行间接免疫过氧化物酶染色。在盲法评估中，将黏附分子表达强度从0至3进行评分。
在未移植的黑褐大鼠心脏中，细胞间黏附分子-1在毛细血管（0.5±0.5）和毛细血管后微静脉（0.5±0.2）内皮上持续低水平表达。在同基因对照中，细胞间黏附分子-1和血管细胞黏附分子-1的表达也很微弱且未被诱导，但在毛细血管内皮上发现II类分子表达明显诱导。大血管的黏附分子染色为阴性。在同种异体移植物中，毛细血管内皮上的细胞间黏附分子-1和血管细胞黏附分子-1，但不包括II类分子，显著上调（p < 0.05）。在毛细血管后微静脉内皮上，移植后5天急性排斥反应期间观察到所有三种分子均有明显诱导（p < 0.05）。同时，炎症白细胞在血管周围间隙中表达高水平的白细胞功能相关抗原-1α链和β链。然而，淋巴细胞上极迟活化抗原-4的表达不存在。在同种异体移植物的动脉和小动脉中，急性排斥反应期间II类分子和血管细胞黏附分子-1，但不包括细胞间黏附分子-1，表达较弱。
我们的结果表明，在大鼠模型的急性心脏同种异体移植排斥反应中，毛细血管后微静脉内皮可能是白细胞外渗的主要部位。
