Spertini O, Luscinskas F W, Kansas G S, Munro J M, Griffin J D, Gimbrone M A, Tedder T F
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115-6084.
J Immunol. 1991 Oct 15;147(8):2565-73.
The human lymphocyte homing receptor, LAM-1, mediates the adhesion of lymphocytes to specialized high endothelial venules (HEV) of peripheral lymph nodes. We now report that LAM-1 is also a major mediator of leukocyte attachment to activated human endothelium. In a novel adhesion assay, LAM-1 was shown to mediate approximately 50% of the adhesion of both lymphocytes and neutrophils to TNF-activated human umbilical vein endothelial cells at 4 degrees C. The contribution of LAM-1 to leukocyte adhesion was only detectable when the assays were carried out under rotating (nonstatic) conditions, suggesting that LAM-1 is involved in the initial attachment of leukocytes to endothelium. In this assay at 37 degrees C, essentially all lymphocyte attachment to endothelium was mediated by LAM-1, VLA-4/VCAM-1, and the CD11/CD18 complex, whereas neutrophil attachment was mediated by LAM-1, endothelial-leukocyte adhesion molecule-1, and CD11/CD18. Thus, multiple receptors are necessary to promote optimal leukocyte adhesion to endothelium. LAM-1 also appeared to be involved in optimal neutrophil transendothelial migration using a videomicroscopic in vitro transmigration model system. LAM-1-dependent leukocyte adhesion required the induction and surface expression of a neuraminidase-sensitive molecule that was expressed for at least 24 h on activated endothelium. Expression of the LAM-1 ligand by endothelium was optimally induced by LPS and the proinflammatory cytokines TNF-alpha and IL-1 beta, whereas IFN-gamma and IL-4 induced lower levels of expression. The LAM-1 ligand on HEV and cytokine treated endothelium may be similar carbohydrate-containing molecules, because phosphomannan monoester core complex from yeast Hansenula hostii cell wall blocked binding of lymphocytes to both cell types, and identical epitopes on LAM-1-mediated lymphocyte attachment to HEV and activated endothelium. Thus, LAM-1 and its inducible endothelial ligand constitute a new pair of adhesion molecules that may regulate initial leukocyte/endothelial interactions at sites of inflammation.
人类淋巴细胞归巢受体LAM-1介导淋巴细胞与外周淋巴结特化的高内皮微静脉（HEV）的黏附。我们现在报告，LAM-1也是白细胞黏附于活化的人内皮细胞的主要介质。在一项新型黏附试验中，结果显示在4℃时，LAM-1介导了淋巴细胞和中性粒细胞与肿瘤坏死因子（TNF）激活的人脐静脉内皮细胞约50%的黏附。只有在旋转（非静态）条件下进行试验时，才能检测到LAM-1对白细胞黏附的作用，这表明LAM-1参与白细胞与内皮细胞的初始黏附。在该试验中，在37℃时，基本上所有淋巴细胞与内皮细胞的黏附均由LAM-1、VLA-4/VCAM-1和CD11/CD18复合物介导，而中性粒细胞的黏附则由LAM-1、内皮细胞-白细胞黏附分子-1和CD11/CD18介导。因此，需要多种受体来促进白细胞与内皮细胞的最佳黏附。使用视频显微镜体外迁移模型系统，LAM-1似乎也参与中性粒细胞的最佳跨内皮迁移。依赖LAM-1的白细胞黏附需要诱导并在活化的内皮细胞表面表达一种对神经氨酸酶敏感的分子，该分子在活化的内皮细胞上至少表达24小时。内皮细胞对LAM-1配体的表达在脂多糖（LPS）以及促炎细胞因子TNF-α和IL-1β的作用下诱导最为明显，而干扰素-γ（IFN-γ）和白细胞介素-4（IL-4）诱导的表达水平较低。HEV和细胞因子处理的内皮细胞上的LAM-1配体可能是相似的含碳水化合物分子，因为来自汉逊酵母细胞壁的磷酸甘露聚糖单酯核心复合物可阻断淋巴细胞与这两种细胞类型的结合，并且LAM-1介导的淋巴细胞与HEV和活化内皮细胞黏附的表位相同。因此，LAM-1及其可诱导的内皮配体构成了一对新的黏附分子，它们可能在炎症部位调节白细胞/内皮细胞的初始相互作用。
