ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE-1 - AN INDUCIBLE RECEPTOR FOR NEUTROPHILS RELATED TO COMPLEMENT REGULATORY PROTEINS AND LECTINS
ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE-1 - AN INDUCIBLE RECEPTOR FOR NEUTROPHILS RELATED TO COMPLEMENT REGULATORY PROTEINS AND LECTINS
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DOI：
10.1126/science.2466335
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发表时间：
1989-03-03
期刊：
影响因子：
56.9
通讯作者：
SEED, B
中科院分区：
文献类型：
--
作者：
BEVILACQUA, MP;STENGELIN, S;SEED, B
白细胞与血管内皮的黏附是炎症和某些血管疾病过程中的关键步骤。内皮白细胞黏附分子 - 1（ELAM - 1）是一种由细胞因子激活的内皮细胞表达的细胞表面糖蛋白，介导血液中性粒细胞的黏附。现在通过在COS细胞中的瞬时表达已经分离出了ELAM - 1的全长互补DNA（cDNA）。用ELAM - 1克隆转染的细胞表达一种可被两种ELAM - 1特异性单克隆抗体（H4/18和H18/7）识别的表面结构，并支持分离的人中性粒细胞和早幼粒细胞系HL - 60的黏附。在培养的人内皮细胞中，ELAM - 1转录本的表达由细胞因子诱导，在2到4小时达到最大值，并在24小时内下降；ELAM - 1蛋白的细胞表面表达与mRNA的表达平行。ELAM - 1的一级序列预测有一个氨基末端凝集素样结构域、一个表皮生长因子（EGF）结构域以及六个与在补体调节蛋白中发现的相关的串联重复基序（每个约60个氨基酸）。在MEL - 14淋巴细胞表面归巢受体以及颗粒膜蛋白140中也发现了类似的结构域结构，颗粒膜蛋白140是血小板和内皮分泌颗粒的一种膜糖蛋白，可被凝血酶和其他刺激物迅速（<5分钟）动员到细胞表面。因此，ELAM - 1可能是一个新兴的细胞表面分子基因家族的成员，该家族参与血管壁和血液界面的炎症和免疫事件的调节。
Focal adhesion of leukocytes to the blood vessel lining is a key step in inflammation and certain vascular disease processes. Endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell surface glycoprotein expressed by cytokine-activated endothelium, mediates the adhesion of blood neutrophils. A full-length complementary DNA (cDNA) for ELAM-1 has now been isolated by transient expression in COS cells. Cells transfected with the ELAM-1 clone express a surface structure recognized by two ELAM-1 specific monoclonal antibodies (H4/18 and H18/7) and support the adhesion of isolated human neutrophils and the promyelocytic cell line HL-60. Expression of ELAM-1 transcripts in cultured human endothelial cells is induced by cytokines, reaching a maximum at 2 to 4 hours and decaying by 24 hours; cell surface expression of ELAM-1 protein parallels that of the mRNA. The primary sequence of ELAM-1 predicts an amino-terminal lectin-like domain, an EGF domain, and six tandem reptitive motifs (about 60 amino acids each) related to those found in complement regulatory proteins. A similar domain structure is also found in the MEL-14 lymphocyte cell surface homing receptor, and in granule-membrane protein 140, a membrane glycoprotein of platelet and endothelial secretory granules that can be rapidly mobilized (< 5 minutes) to the cell surface by thrombin and other stimuli. Thus, ELAM-1 may be a member of a nascent gene family of cell surface molecules involved in the regulation of inflammatory and immunological events at the interface of vessel wall and blood.