title: Colonic epithelial cells express specific ligands for mucosal macrophage immunosuppressive receptors siglec-7 and -9.
abstract: Immune cells are known to express specific recognition molecules for cell surface glycans. However, mechanisms involved in glycan-mediated cell-cell interactions in mucosal immunity have largely been left unaccounted for. We found that several glycans preferentially expressed in nonmalignant colonic epithelial cells serve as ligands for sialic acid-binding Ig-like lectins (siglecs), the immunosuppressive carbohydrate-recognition receptors carried by immune cells. The siglec ligand glycans in normal colonic epithelial cells included disialyl Lewis(a), which was found to have binding activity to both siglec-7 and -9, and sialyl 6-sulfo Lewis(x), which exhibited significant binding to siglec-7. Expression of these siglec-7/-9 ligands was impaired upon carcinogenesis, and they were replaced by cancer-associated glycans sialyl Lewis(a) and sialyl Lewis(x), which have no siglec ligand activity. When we characterized immune cells expressing siglecs in colonic lamina propriae by flow cytometry and confocal microscopy, the majority of colonic stromal immune cells expressing siglec-7/-9 turned out to be resident macrophages characterized by low expression of CD14/CD89 and high expression of CD68/CD163. A minor subpopulation of CD8(+) T lymphocytes also expressed siglec-7/-9. Siglec-7/-9 ligation suppressed LPS-induced cyclooxygenase-2 expression and PGE(2) production by macrophages. These results suggest that normal glycans of epithelial cells exert a suppressive effect on cyclooxygenase-2 expression by resident macrophages, thus maintaining immunological homeostasis in colonic mucosal membranes. Our results also imply that loss of immunosuppressive glycans by impaired glycosylation during colonic carcinogenesis enhances inflammatory mediator production.
authors.affiliation: Department of Molecular Pathology, Aichi Cancer Center, Research Institute, Nagoya 464-8681, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Sakuma
authors.forename: Yuki I
authors.initials: YI
authors.lastname: Kawamura
authors.forename: Mineko
authors.initials: M
authors.lastname: Izawa
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Ohmori
authors.forename: Motoaki
authors.initials: M
authors.lastname: Mitsuki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Yamaji
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: Akemi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D006031:Glycosylation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D037102:Lectins / Q000096:biosynthesis / Q000276:immunology*; D007983:Lewis Blood Group Antigens; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009844:Oligosaccharides / Q000276:immunology / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018836:Inflammation Mediators; D037102:Lectins; D007983:Lewis Blood Group Antigens; C494219:Lewis a oligosaccharide; D008070:Lipopolysaccharides; D009844:Oligosaccharides; C402206:SIGLEC7 protein, human; C412227:SIGLEC9 protein, human; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human