CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells

T. W. Kuijpers*, M. Hoogerwerf, L. J.W. Van der Laan, G. Nagel, C. E. Van der Schoot, F. Grunert, D. Roos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

168 Citations (Scopus)

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 (SLe(x)) structure. The selectin LAM-1 (or LECAM-1) has been described as one of the SLe(x)-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 neutrophils-known as the nonspecific cross-reacting antigens (NCAs)-are involved in neutrophil adherence to monolayers of IL-1-β-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-β-activated 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-β-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.

Original languageEnglish
Pages (from-to)457-465
Number of pages9
JournalJournal of Cell Biology
Volume118
Issue number2
DOIs
Publication statusPublished - 15 Jul 1992
Externally publishedYes

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