Duijvestijn A M, Kerkhove M, Bargatze R F, Butcher E C
J Immunol. 1987 Feb 1;138(3):713-9.
Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.
内皮细胞通过调节白细胞进入淋巴组织和炎症部位，在免疫反应中发挥重要作用。作为分析与这种免疫功能相关的内皮细胞特化的初步方法，我们制备了针对小鼠淋巴结内皮的单克隆抗体（MAB）。选择了三种抗体：MECA - 20，可识别淋巴器官和非淋巴器官中所有血管的内皮；MECA - 217，可对大型弹性动脉的内皮进行染色，但在小血管中，它对淋巴器官以及暴露于外源性抗原的组织（如皮肤和子宫）内的毛细血管后微静脉具有特异性；还有MECA - 325，该抗体对专门的高内皮微静脉（HEV）具有特异性，HEV可控制淋巴细胞归巢至淋巴结和派伊尔结。MECA - 325未能对任何测试的非淋巴器官中的血管进行染色。对淋巴结冰冻切片中的HEV以及悬浮液中分离的高内皮细胞进行免疫过氧化物酶研究表明，所有三种抗体识别的抗原均在细胞表面表达；MECA - 20和MECA - 325所定义的抗原也存在于细胞质中。为了研究这些MAB所定义的抗原与淋巴外免疫反应相关的调节情况，我们评估了它们在诱导的皮下肉芽肿（作为慢性炎症模型）中的表达。在肉芽肿发育的最初几天，MECA - 217就已对其中的小血管进行了染色。相比之下，MECA - 325直到大约1周后才检测到毛细血管后微静脉（其经常表现出HEV的形态特征），这与包括众多淋巴细胞在内的持续性单核细胞浸润的发展同步。MECA - 325抗原在支持淋巴细胞在淋巴和淋巴外部位流动的血管内皮上的选择性出现表明，该抗原可能在淋巴细胞外渗过程中发挥重要作用。淋巴器官和炎症特异性微血管抗原的证明为内皮细胞与免疫刺激相关的复杂特化提供了直接证据，并支持微血管分化可能在局部免疫反应中起重要作用的概念。
