Virji M, Makepeace K, Ferguson D J, Watt S M
Department of Paediatrics, University of Oxford, John Radcliffe Hospital, UK.
Mol Microbiol. 1996 Dec;22(5):941-50. doi: 10.1046/j.1365-2958.1996.01551.x.
Opa protein-expressing pathogenic neisseriae interact with CD66a-transfected COS (African green monkey kidney) and CHO (Chinese hamster ovary) cells. CD66a (BGP) is a member of carcinoembryonic antigen (CEA, CD66) family. The interactions occur at the N-terminal domain of CD66a, a region that is highly conserved between members of the CEA subgroup of the CD66 family. In this study, we have investigated the roles of CD66 expressed on human epithelial cells and polymorphonuclear phagocytes (PMNs) in adhesion mediated via Opa proteins. Using human colonic (HT29) and lung (A549) epithelial cell lines known to express CD66 molecules, we show that these receptors are used by meningococci. A monoclonal antibody, YTH71.3, against the N-terminal domain of CD66, but not 3B10 directed against domains, A1/ B1, inhibited meningococcal adhesion to host cells. When acapsulate bacteria expressing Opa proteins were used, large numbers of bacteria adhered to HT29 and A549 cells. In addition, both CD66a-transfected CHO cells and human epithelial cells were invaded by Opa-expressing meningococci, suggesting that epithelial cell invasion may occur via Opa-CD66 interactions. In previous studies we have shown that serogroup A strain C751 expresses three Opa proteins, all of which mediate non-opsonic interactions with neutrophils. We have examined the mechanisms of these interactions using antibodies and soluble chimeric receptors. The results indicate that the nature of their interactions with purified CD66a molecules and with CD66 on neutrophils is alike and that these interactions occur at the N-terminal domain of CD66. Thus, the Opa family of neisserial ligands may interact with several members of the CD66 family via their largely conserved N-terminal domains.
表达Opa蛋白的致病性奈瑟菌与转染了CD66a的COS（非洲绿猴肾）细胞和CHO（中国仓鼠卵巢）细胞相互作用。CD66a（BGP）是癌胚抗原（CEA，CD66）家族的成员。这些相互作用发生在CD66a的N端结构域，该区域在CD66家族CEA亚组成员之间高度保守。在本研究中，我们研究了人类上皮细胞和多形核吞噬细胞（PMN）上表达的CD66在通过Opa蛋白介导的黏附中的作用。使用已知表达CD66分子的人结肠（HT29）和肺（A549）上皮细胞系，我们发现脑膜炎奈瑟菌利用这些受体。一种针对CD66 N端结构域的单克隆抗体YTH71.3，而不是针对A1/B1结构域的3B10，抑制了脑膜炎奈瑟菌对宿主细胞的黏附。当使用表达Opa蛋白的无荚膜细菌时，大量细菌黏附到HT29和A549细胞上。此外，表达Opa的脑膜炎奈瑟菌侵袭了转染CD66a的CHO细胞和人类上皮细胞，这表明上皮细胞侵袭可能通过Opa-CD66相互作用发生。在先前的研究中，我们表明A群菌株C751表达三种Opa蛋白，所有这些蛋白都介导与中性粒细胞的非调理相互作用。我们使用抗体和可溶性嵌合受体研究了这些相互作用的机制。结果表明，它们与纯化的CD66a分子以及中性粒细胞上的CD66的相互作用性质相似，并且这些相互作用发生在CD66的N端结构域。因此，奈瑟菌配体的Opa家族可能通过其高度保守的N端结构域与CD66家族的几个成员相互作用。
