Two new synthetic peptides from the N-domain of CEACAM1 (CD66a) stimulate neutrophil adhesion to endothelial cells.
Four members of the carcinoembryonic antigen family, CEACAMs 1, 3, 6, and 8, are expressed on human neutrophils and can trigger an activation signal that increases neutrophil adhesion to human umbilical vein endothelial cell (HUVEC) monolayers. To identify active sites on CEACAM1, we previously performed molecular modeling using IgG and CD4 as models, and 28 peptides of 14 amino acids in length were synthesized that were predicted to be present at loops and turns between β-sheets. Three peptides, each from the N-terminal domain, increased neutrophil adhesion to HUVEC monolayers and upregulated cell-surface CD11b/CD18 expression on neutrophils. In our earlier study, one N-domain peptide (CD66a-7) was not successfully synthesized, and another N-domain peptide (CD66a-6) was not soluble in the assay system. In the present study, we have now successfully synthesized CD66a-7, and a new peptide (CD66a-6L), that is a modification of the peptide that was insoluble in the earlier study. Both of these new peptides increased neutrophil adhesion to HUVEC monolayers. Importantly, the amino acid sequence of CD66a-7 is identical to the homologous peptides from CEACAMs 3, 5, and 6, but differs from the homologous peptide of CEACAM8, which was not active in this system. CD66a-6L is identical to the homologous peptide from CEACAM6. The data suggest that peptide motifs from at least five regions of the N-terminal domain of CEACAM1 are involved in the interaction of CEACAM1 with other ligands and can initiate signal transduction in neutrophils. Some of these active peptides are identical to homologous regions of other CEACAMs.
Skubitz
Keith M
KM
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA. skubi001@umn.edu
Skubitz
Amy P N
AP
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D009504:Neutrophils / Q000166:cytology*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D015703:Antigens, CD; C069847:CD66 antigens; D015815:Cell Adhesion Molecules; D010455:Peptides