L1 adhesion molecule on human lymphocytes and monocytes: Expression and involvement in binding to alpha v beta 3 integrin
L1 adhesion molecule on human lymphocytes and monocytes: Expression and involvement in binding to alpha v beta 3 integrin
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DOI：
10.1002/eji.1830261035
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发表时间：
1996-10-01
影响因子：
5.4
通讯作者：
Altevogt, P
中科院分区：
文献类型：
--
作者：
Ebeling, O;Duczmal, A;Altevogt, P
L1粘附分子是免疫球蛋白（IG）超家族的成员，最初在神经系统中鉴定，其包含六个Ig样结构域。除了已知的L1-L1同型相互作用，L1最近被证明在小鼠中与极晚期抗原（VLA）-5结合，在人类中与α v β 3结合。第六个IG结构域是该功能的关键。我们现在证明，人外周血CD 4（+）T淋巴细胞、单核细胞和B淋巴细胞表达LI，但不表达CD 8（+）T淋巴细胞。当与T淋巴细胞上α v β 3的另一种配体CD 31的表达相比时，只有一小部分细胞是CD 31（+）L1（+）双阳性。L1也在人单核细胞和淋巴样turner细胞系的表面上检测到，并显示具有类似于220 kDa的分子量，类似于神经母细胞瘤细胞上存在的分子。并对人LI的第六个IG结构域作为整合素配体的功能进行了研究。使用衍生自第六IG结构域的含RGD的肽以及L1的第六IG结构域和人IgG 1的Fe部分的融合蛋白（fi，LI-Fc），我们证明了人MED-B1（α v β 3（In），α 5 β 1（lo））肿瘤细胞的结合，并且这种结合被α v特异性mAb阻断。相比之下，人Nalm-6细胞（α v β（lo），α 5 β 1（hi））不与6.L1-Fe融合蛋白结合。MED-BI细胞也可以用6.L1-Fc融合蛋白染色。我们的研究结果表明，人类L1主要结合α v β 3，它的存在对白细胞的粘附和迁移可能是重要的。
The L1 adhesion molecule is a member of the immunoglobulin (Ig) superfamily initially identified in the nervous system which contains six Ig-Iike domains. Besides the known L1-L1 homotypic interaction, L1 was recently shown to bind to very late antigen (VLA)-5 in the mouse and alpha v beta 3 in the human. The sixth Ig domain is critical for this function, We now demonstrate that human CD4(+) peripheral blood T lymphocytes, monocytes and B lymphocytes, but not CD8(+) Tlymphocytes, express LI. When compared to the expression of CD31, another ligand for alpha v beta 3 on T lymphocytes, only a small proportion of cells were CD31(+)L1(+) double positive. L1 was also detected on the surface of human monocytic and lymphoid turner lines and was shown to have a molecular mass of similar to 220 kDa, similar to the molecule present on neuroblastoma cells. The function of the sixth Ig domain of human LI as an integrin ligand was also investig ated. Using an RGD-containing peptide derived from the sixth Ig domain as well as a fusion protein of the sixth Ig domain of L1 and the Fe Portion of human IgG1 (fi,LI-Fc), we demonstrated the binding of human MED-B1 (alpha v beta 3(In), alpha 5 beta 1(lo)) tumor cells and this binding was blocked by alpha v-specific mAb. In contrast, human Nalm-6 cells (alpha v beta(lo), alpha 5 beta 1(hi)) did not bind to the 6.L1-Fe fusion protein. MED-BI cells could also be stained with the 6.L1-Fc fusion protein. Our results suggest that human L1 binds predominantly to alpha v beta 3 and that its presence on leukocytes could be important for adhesion and migration.