CD66A, CD66B, CD66C, AND CD66D EACH INDEPENDENTLY STIMULATE NEUTROPHILS

Four members of the carcinoembryonic antigen family, CD66a, CD66b, CD6 6c, and CD66d, are expressed on human neutrophils. In neutrophils thes e proteins are activation antigens in that their surface expression is increased following stimulation. To examine their potential role in n eutrophil signaling, the effects on neutrophil adhesion to human umbil ical 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 veil endothelial cell monolayer s, This increase in neutrophil adhesion caused by CD66 antibodies Tvas blocked by a CD18 antibody and associated with up-regulation of CD11/ CD18 on the neutrophil surface, This increase ill neutrophil adhesion required physiological extracellular calcium concentrations at or near the time of CD66 antibody binding to the neutrophil. The incubation o f CD66 antibodies with neutrophils in the absence of calcium for 10 mi n before repletion of calcium resulted in no increase in neutrophil ad hesion. Tile data suggest that CD66a, CD66b, CD66c, and CD66d antibody binding to the neutrophil surface triggers a transient activation sig nal that requires extracellular calcium and regulates the adhesive act ivity of CD11/CD18, Sequential desensitization experiments indicated t hat CD66a, CD66b, CD66c, and CD66d can each independently transmit sig nals in neutrophils.