Nicoll Gavin, Avril Tony, Lock Kevin, Furukawa Koichi, Bovin Nicolai, Crocker Paul R
The School of Life Sciences, Wellcome Trust Biocentre, University of Dundee, GB.
Eur J Immunol. 2003 Jun;33(6):1642-8. doi: 10.1002/eji.200323693.
Siglec-7 is a sialic acid binding receptor with inhibitory potential, expressed on human NK cells and monocytes. It has an unusual binding preference for alpha2,8-linked disialic acids, such as those displayed by ganglioside GD3. Here we have investigated whether siglec-7-GD3 interactions are able to modulate NK cell cytotoxicity. Using synthetic polyacrylamide glycoprobes, siglec-7 was found to be masked at the NK cell surface but it could be unmasked by sialidase treatment of NK cells. GD3 synthase-transfected P815 target cells expressed high levels of GD3 and bound strongly to recombinant siglec-7-Fc protein. Surprisingly, GD3 synthase-transfected P815 cells were killed more effectively by untreated cells in a siglec-7-independent manner. However, following sialidase treatment of NK cells, a siglec-7-dependent inhibition of killing was observed. These findings have important implications for NK cell cytotoxicity against tumor cells like melanoma that express high levels of GD3 ganglioside.
唾液酸结合免疫球蛋白样凝集素7（Siglec-7）是一种具有抑制潜能的唾液酸结合受体，在人类自然杀伤细胞（NK细胞）和单核细胞上表达。它对α2,8-连接的二唾液酸具有不同寻常的结合偏好，比如神经节苷脂GD3所呈现的那些二唾液酸。在此，我们研究了Siglec-7与GD3的相互作用是否能够调节NK细胞的细胞毒性。使用合成的聚丙烯酰胺糖探针，发现Siglec-7在NK细胞表面被掩盖，但可通过对NK细胞进行唾液酸酶处理而使其暴露。转染了GD3合酶的P815靶细胞表达高水平的GD3，并与重组Siglec-7-Fc蛋白强烈结合。令人惊讶的是，转染了GD3合酶的P815细胞被未处理的细胞以不依赖Siglec-7的方式更有效地杀伤。然而，在对NK细胞进行唾液酸酶处理后，观察到了Siglec-7依赖性的杀伤抑制。这些发现对于NK细胞对表达高水平GD3神经节苷脂的肿瘤细胞（如黑色素瘤）的细胞毒性具有重要意义。
