title: CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils.
abstract: Four members of the carcinoembryonic antigen family, CD66a, CD66b, CD66c, and CD66d, are expressed on human neutrophils. In neutrophils these proteins are activation antigens in that their surface expression is increased following stimulation. To examine their potential role in neutrophil signaling, the effects on neutrophil adhesion to human umbilical vein endothelial cells of a panel of well-characterized CD66 mAbs was tested. CD66a, CD66b, CD66c, and CD66d antibodies each increased neutrophil adhesion to human umbilical vein endothelial cell monolayers. This increase in neutrophil adhesion caused by CD66 antibodies was blocked by a CD18 antibody and associated with up-regulation of CD11/CD18 on the neutrophil surface. This increase in neutrophil adhesion required physiological extracellular calcium concentrations at or near the time of CD66 antibody binding to the neutrophil. The incubation of CD66 antibodies with neutrophils in the absence of calcium for 10 min before repletion of calcium resulted in no increase in neutrophil adhesion. The data suggest that CD66a, CD66b, CD66c, and CD66d antibody binding to the neutrophil surface triggers a transient activation signal that requires extracellular calcium and regulates the adhesive activity of CD11/CD18. Sequential desensitization experiments indicated that CD66a, CD66b, CD66c, and CD66d can each independently transmit signals in neutrophils.
authors.affiliation: Department of Medicine, University of Minnesota Medical School, Minneapolis, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Skubitz
authors.forename: K D
authors.initials: KD
authors.lastname: Campbell
authors.forename: A P
authors.initials: AP
authors.lastname: Skubitz
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000276:immunology / Q000502:physiology*; D000943:Antigens, Differentiation / Q000276:immunology / Q000502:physiology*; D000951:Antigens, Neoplasm; D018821:CD18 Antigens / Q000276:immunology / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002272:Carcinoembryonic Antigen / Q000276:immunology / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000502:physiology; D058851:GPI-Linked Proteins; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen / Q000276:immunology / Q000502:physiology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D018821:CD18 Antigens; C069847:CD66 antigens; C075729:CEACAM3 protein, human; C504117:CEACAM6 protein, human; C504120:CEACAM8 protein, human; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D007140:Immunoglobulin Fab Fragments; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002118:Calcium