Disease relevance of CEACAM8

• Neutrophils from a patient severely affected by paroxysmal nocturnal hemoglobinuria completely lacked expression of NCA-95 and NCA-90 [1].
• CD66b may be interesting as a marker for kidney and corpus carcinomas, for which good markers are not yet available [2].
• CGM6 transcripts were only found thus far in leukocytes of chronic myeloid leukemia patients, in normal bone marrow, and in marginal amounts in normal granulocytes [3].
• Immunocytochemical staining with monoclonal antibodies (MAb) against carcinoembryonic antigen (CEA) and nonspecific cross-reacting antigen 95 (NCA 95) were used to help in discriminating carcinoma in situ from papillary duct hyperplasia [4].
• The epitope recognized by MAb 250 (present on CEA and NCA 95) was expressed in all but one pancreatic ductal adenocarcinoma and ampullary carcinoma (42/43) [5].

High impact information on CEACAM8

• Using OpaI as the prototype, the relative ability of the transfected HeLa cell lines to support adherence was (CEA = BGPa >CGM1a >NCA >>CGM6 = Neo) [6].
• We also compared the adherence and invasion by Opa+ bacteria of CD66 transfected HeLa cells: HeLa-BGPa, HeLa-CGM6, HeLa-NCA, HeLa-CGM1a, HeLa-CEA, and HeLa-Neo serving as negative control [6].
• In addition, forced expression of C/EBPepsilon in the U937 myelomonoblastic leukemia cells mimicked terminal granulocytic differentiation, including morphologic changes, increased CD11b/CD66b expression, and induction of secondary granule protein expression [7].
• 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 [8].
• We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1 beta by stimulated monocytes was positively associated with the relative loss [9].

Chemical compound and disease context of CEACAM8

• Consistent with the hypothesis, the HIV-1 protease inhibitors enhanced the ability of ATRA to inhibit growth and induce differentiation of HL-60 and NB4 myeloid leukemia cells, as measured by expression of CD11b and CD66b cell surface antigens, as well as reduction of nitroblue tetrazolium [10].
• However, their cells had a normal expression of other phosphatidylinositol (PI)-linked membrane glycoprotein (CD24, CD67, and CLB gran/5 antigens), ruling out the existence of a PI-linkage defect, such as paroxysmal nocturnal hemoglobinuria [11].
• Immunoscintigraphy with a technetium-99m murine monoclonal IgG1 antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body [12].

Biological context of CEACAM8

• Identification and comparison of residues critical for cell-adhesion activities of two neutrophil CD66 antigens, CEACAM6 and CEACAM8 [13].
• Furthermore, the nanoelectrospray mass spectrometry (MS/MS) analysis of the two selected tryptic peptides of the protein revealed two amino acid sequences corresponding to residues 79-98 and 199-207 of the CGM6 gene product [14].
• Cysteine-containing sequences for CEA and NCA-95 show up to 95% sequence homology, and the CEA sequences also show internal sequence homologies [15].
• We have analyzed a cosmid containing the complete CGM6 gene [16].
• CD66b expression is first seen in the fetal liver on day 12.5 of mouse embryonic development, and it first appears in the bone marrow at day 17 [16].

Anatomical context of CEACAM8

• We demonstrated that CEACAM1 and CEACAM8 are physically associated in human granulocytes [17].
• The NH(2)-terminal domain (N-domain) of CEACAM6 expressed on a CHO cell was suggested to bind the N-domain of CEACAM6 or CEACAM8 on the opposing cell [13].
• The cell adhesion mediated by CD66b and CD66c may play a role in interaction between neutrophils or between neutrophils and epithelial cells expressing CD66c in vivo [18].
• However, five B-lineage ALLs showed conflicting data on the binding patterns of two, on leukocytes specifically NCA-95 recognizing antibodies suggesting either expression of unknown forms of NCA-95 or NCA-50/90 or of a yet unknown member of the CEA family in these ALL cells [19].
• NCA-95 was not expressed in 91% of the B-lineage ALLs, in T-lineage ALLs and in the B-cell lines [19].

Associations of CEACAM8 with chemical compounds

• Ligation of CGM6 or NCA90 alone did not cause activation of the neutrophil in any of the assays used and did not cause priming of fMLP-induced oxidant production even when a secondary cross-linking reagent was used [20].
• In addition, associated tyrosine kinase activity may play a role in signal transduction from CD66a, CD66b, and CD66c to regulate other cell functions [21].
• All samples of synovial fluid PMN exhibited an additional increase in the expression of CD66a, CD66b, and CD66c when stimulated with phorbol myristate acetate in vitro [22].
• Reduced technetium 99m labelled NCA-95/CEA-antibody uptake in liver due to gentle antibody reconstitution. Technical note [23].
• On the basis of previous work with various monoclonal antibodies (Mab) raised against carcino-embryonic antigen (CEA), the anti-CEA Mab 47 was identified which selectively reacted with a surface glycoprotein (95 kDa; NCA 95) of normal human granulocytes [24].

Physical interactions of CEACAM8

• The CEACAM1/CEACAM8 complex in human cells might accordingly play a similar role as CEACAM1-L/CEACAM1-S dimers known to occur in rat cells [17].

Regulatory relationships of CEACAM8

• CD66a, and CD66b were expressed on RA and OA ST myeloid cells but not on normal ST lining cells and interstitial macrophages, suggesting that these antigens may be specific markers of diseased compared to normal ST macrophages (P < 0.05) [25].
• Specific Abs against VAMP-2 inhibited Ca(2+) and GTP-gamma-S-induced exocytosis of CD66b-enriched specific and tertiary granules, but did not affect exocytosis of CD63-enriched azurophilic granules, in electropermeabilized neutrophils [26].
• Using an immunofluorescence staining procedure, cross-linking of CD66b induced the redistribution of CD11b on neutrophils with distinct areas of CD11b clustering via a process susceptible of inhibition by D-mannose [27].

Other interactions of CEACAM8

• Preparation and characterization of two human carcinoembryonic antigen family proteins of neutrophils, CD66b and c, in silkworm larvae [28].
• Cross-linking of the carcinoembryonic antigen-like glycoproteins CD66 and CD67 induces neutrophil aggregation [1].
• Other members of this family, NCA95, NCA90 and NCA55, which are also found in neutrophils, do not express the CD15 antigen [29].
• Administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals resulted in an increased content of CEACAM8 in neutrophils on day 1, which decreased on day 4 [30].
• However, the content of CEACAM8 in the light membrane fraction was increased on day 4, possibly due to the stimulation by induced secondary cytokines, such as tumour necrosis factor-alpha (TNF-alpha) [30].

Analytical, diagnostic and therapeutic context of CEACAM8

• The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies [31].
• SDS-PAGE analysis of immunoprecipitates from the granules revealed that NCA-95 (CD66c, NCA-50/90) exists predominantly in the azurophil granule-enriched fraction [32].
• An enzyme-linked immunosorbent assay for human carcinoembryonic antigen-related cell adhesion molecule 8, a biological marker of granulocyte activities in vivo [33].
• These mice could provide a model for transplantation and for inflammation studies using CD66b as a granulocyte-specific marker [16].
• 5. Northern blot analysis showed that CD66b transcripts are confined to the bone marrow of adult mice, whereas immunohistochemistry also showed CD66b-positive granulocytes in the spleen, thymus, and lungs [16].

References