title: Novel synthesized trimannose conjugate induces endocytosis and expression of immunostimulatory molecules in monocytic leukemia cells.
abstract: Macrophage mannose receptor (MMR) recognizes the pattern of carbohydrates exposed on microorganisms and mediates endocytosis in macrophages. We have synthesized glycoconjugate cationic polymers carrying 3,6-branched alpha-D-mannoside, a trimannose conjugate (TMC) with a high affinity for mannose-specific lectins. Culture with 10 microM TMC for 6 hours induced adhesion and aggregation in NKM-1, a human myelomonocytic leukemia cell line. TMC also stimulated the accumulation of fluorescein isothiocyanate (FITC)-dextran (FITC-DX). This accumulation seemed to be mediated by endocytosis via MMR because mannan, which specifically binds to MMR, inhibited FITC-DX accumulation. Expression of CD14, adhesion molecules, and costimulatory molecules was induced for 24 hours in NKM-1 and in fresh leukemia blasts from 4 patients with acute myeloid leukemia (AML) M4 and M5 subtypes (French-American-British classification). To clarify the binding mechanism, we compared mannose conjugates and a monomer of mannose regarding their effects on endocytosis and enhancement of CD14 and CD86 expression. A polymer of monomannose clusters with a lower affinity for lectins slightly stimulated exdocytosis, whereas a monomer of trimannose had no effect. These findings suggest that concatenation between MMR and TMC may play an important role in the activation of monocytic leukemia cells. TMC may become a good candidate to target MMRs of leukemia cells.
authors.affiliation: First Department of Internal Medicine, Graduate School of Medicine, Nagoya University, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kanbe
authors.forename: N
authors.initials: N
authors.lastname: Emi
authors.forename: A
authors.initials: A
authors.lastname: Abe
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000378:metabolism*; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism; D051940:B7-2 Antigen; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D003911:Dextrans / Q000493:pharmacokinetics; D004705:Endocytosis / Q000187:drug effects*; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type; D007951:Leukemia, Myeloid / Q000276:immunology / Q000473:pathology*; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000737:chemistry; D008358:Mannose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology; D014312:Trisaccharides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D003911:Dextrans; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D014312:Trisaccharides; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate; D008358:Mannose