title: CD66: role in the regulation of neutrophil effector function.
abstract: 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.
authors.affiliation: Unit of Respiratory Medicine, University of Edinburgh Medical School, Scotland.
authors.forename: S C
authors.initials: SC
authors.lastname: Stocks
authors.forename: M H
authors.initials: MH
authors.lastname: Ruchaud-Sparagano
authors.forename: M A
authors.initials: MA
authors.lastname: Kerr
authors.forename: F
authors.initials: F
authors.lastname: Grunert
authors.forename: C
authors.initials: C
authors.lastname: Haslett
authors.forename: I
authors.initials: I
authors.lastname: Dransfield
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000494:pharmacology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D003429:Cross Reactions / Q000276:immunology; D007152:Immunologic Capping / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology*; D017452:Receptors, IgG / Q000276:immunology; D016897:Respiratory Burst / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D008562:Membrane Glycoproteins; D017452:Receptors, IgG