Stocks S C, Ruchaud-Sparagano M H, Kerr M A, Grunert F, Haslett C, Dransfield I
Unit of Respiratory Medicine, University of Edinburgh Medical School, Scotland.
Eur J Immunol. 1996 Dec;26(12):2924-32. doi: 10.1002/eji.1830261218.
Neutrophils express several heavily glycosylated carcinoembryonic antigen (CEA)-related glycoproteins (CD66 antigens) which have been implicated in adhesion to E-selectin and as receptors for the lectins galectin 3 and bacterial type-1 fimbriae. The role of the CD66 antigens in neutrophil effector function was examined using non-cross-reacting and cross-reacting domain-mapped CD66 monoclonal antibody (mAb), which recognize epitopes on biliary glycoprotein (BGP; CD66a), CEA gene family member 6 (CGM6; CD66b), nonspecific cross-reacting antigen 90 (NCA90; CD66c) or CGM1 (CD66d). We show that BGP-specific mAb which recognize an AB-domain epitope strongly augment adhesion to fibrinogen by an Fc receptor- and beta2 integrin-dependent mechanism. Co-ligation of BGP with the glycophosphatidylinositol (GPI)-anchored CGM6 and NCA90 also caused increased beta2 integrin-mediated adhesion, receptor clustering and priming of formyl-Met-Leu-Phe (fMLP)-induced oxidant production by neutrophils, but only a small change in expression of L-selectin and CR3 compared to the chemotactic peptide fMLP. Ligation of CGM6 or NCA90 alone did not cause activation of the neutrophil in any of the assays used and did not cause priming of fMLP-induced oxidant production even when a secondary cross-linking reagent was used. We propose that specific cross-linking of neutrophil BGP with CGM6 and NCA90 contributes significantly to the regulation of neutrophil function during neutrophil recruitment.
中性粒细胞表达几种高度糖基化的癌胚抗原（CEA）相关糖蛋白（CD66抗原），这些糖蛋白与E-选择素的黏附有关，并且作为凝集素半乳糖凝集素3和细菌1型菌毛的受体。使用非交叉反应和交叉反应结构域映射的CD66单克隆抗体（mAb）检测CD66抗原在中性粒细胞效应功能中的作用，这些抗体识别胆汁糖蛋白（BGP；CD66a）、CEA基因家族成员6（CGM6；CD66b）、非特异性交叉反应抗原90（NCA90；CD66c）或CGM1（CD66d）上的表位。我们发现，识别AB结构域表位的BGP特异性mAb通过Fc受体和β2整合素依赖性机制强烈增强对纤维蛋白原的黏附。BGP与糖基磷脂酰肌醇（GPI）锚定的CGM6和NCA90的共连接也导致β2整合素介导的黏附增加、受体聚集以及中性粒细胞由甲酰甲硫氨酸亮氨酸苯丙氨酸（fMLP）诱导的氧化剂产生的启动，但与趋化肽fMLP相比，L-选择素和CR3的表达仅有微小变化。单独连接CGM6或NCA90在任何所用检测中均未引起中性粒细胞的激活，即使使用二级交联试剂也未引起fMLP诱导的氧化剂产生的启动。我们提出，中性粒细胞BGP与CGM6和NCA90的特异性交联在中性粒细胞募集过程中对中性粒细胞功能的调节有显著贡献。
