Abstract. Neutrophil adherence to cytokine-activated endothelial cell (EC) monolayers depends on the expression of the endothelial leukocyte adhesion molecule-1 (ELAM-1). The ligand for ELAM-1 is the sialylated Lewis-x antigen (SLe0 structure. The selectin LAM-1 (or LECAM-1) has been described as one of the SLex-presenting glycoproteins involved in neutrophil binding to ELAM-1. Other presenter molecules have not yet been described.Our data demonstrate that the carcinoembryonic antigen (CEA)-like surface molecules on neutrophilsknown as the nonspecific cross-reacting antigens (NCAs)-are involved in neutrophil adherence to monolayers of IL-1-/3-activated EC. The NCAs are recognized by CD66 (NCA-160 and NCA-90) and CD67 (NCA-95). Because NCA-95 and NCA-90 have previously been found to be phosphatidylinositol (PI)-linked, paroxysmal nocturnal hemoglobinuria (PNH) neutrophils (which lack PI-linked surface proteins) were tested as well. PNH neutrophils showed a diminished binding to activated EC. CD66 (on PNH cells still recognizing the transmembrane NCA-160 form) still inhibited the adherence of PNH cells to IL-1-Bactivated EC, but to a limited extent.Soluble CEA(-related) antigens inhibited normal neutrophil adherence as well, whereas neutrophil transmigration was unaffected. Sialidase-treatment as well as CD66 preclearing abolished the inhibitory capacity of the CEA(-related) antigens. The binding of soluble CEA antigens to IL-1-B-pretreated EC was blocked by anti-ELAM-1. These soluble antigens, as well as the neutrophil NCA-160 and NCA-90, both recognized by CD66 antibodies, presented the SLe x determinant.Together, these findings indicate that the CD66 antigens (i.e., NCA-160/NCA-90) function as presenter molecules of the SLe x oligosaccharide structures on neutrophils that bind to ELAM-1 on EC.

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We describe a patient with leucocyte adhesion deficiency (LAD). Clinically, the patient had delayed umbilical cord detachment, omphalitis, impaired wound healing and persistent leucocytosis. The patient had the severe form of LAD, with a total absence of leucocyte cell adhesion molecules (LeuCAMs) and undetectable mRNA for the beta chain, the common subunit of the LeuCAMs. In vitro neutrophil chemotaxis, aggregation and oxygen consumption were severely impaired. In vitro incubation of neutrophils with recombinant human interferon-gamma (rIFN-gamma) showed an increase in oxygen consumption, but no effect on the expression of the LeuCAMs, or the beta chain mRNA. In vivo treatment with IFN-gamma was started. The Fc gamma RI receptor appeared on the neutrophils, the LeuCAMs remained undetectable, while the neutrophil functions remained disturbed. The patient died of surgical complications after 10 weeks of rIFN-gamma treatment. No new infections or side-effects due to rIFN-gamma were observed.