CD66: role in the regulation of neutrophil effector function
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 CGMl (CD66d). We show that BGP-specific mAb which recognize an AB-domain epitope strongly augment adhesion to fibrinogen by an Fc receptor-and p2 integrin-dependent mechanism. Co-ligation of BGP with the glycophosphatidylinositol (GP1)-anchored CGM6 and NCA90 also caused increased p2 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 neutro-Phil BGP with CGM6 and NCA90 contributes significantly to the regulation of neutrophil function
1 Introduction
Neutrophils are rapidly recruited to sites of injury or infection in a process requiring a highly coordinated set of celV cell and cellkytokine interactions involving specialized cell surface molecules that receive these signals and contribute to regulation [l]. Many glycoproteins with a role in celkell communication processes are members of the immunoglobulin superfamily (IgSF) [2], including the TCR and BCR receptor complexes and a number of adhesion molecules expressed on neutrophils and endothelial cells.
The carcinoembryonic antigen (CEA) family is a subfamily of the IgSF. The four distinct CEA gene family products expressed by neutrophils are biliary glycoprotein (BGP), CEA gene-family member 6 (CGM6), nonspecific cross-reacting antigen (NCA90) and CGM1, recognized by CD66a, b, c, or d mAb, respectively [3]. The largest of these, BGP (approximate Mr 180 000), has an N-terminal Ig V-like domain and three Ig C2 domains, subclassified into A l , B1, and A2 domains according to sequence similarity with other CEA family molecules [4, 51. CGM6 (Mr [I 157501