title: Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced differentiation toward dendritic cells.
abstract: IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this study, we explored the effect of GAGs on the IL-4-induced differentiation of monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated with hampered IL-4-induced DC differentiation as evidenced by lower expression of DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4-induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC, CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group (heparin) and specific O sulfates (CSB and heparin). Together, these data demonstrate that monocyte cell surface chondroitin sulfates play an important role in the IL-4-driven differentiation of monocytes into DCs.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Els
authors.initials: E
authors.lastname: den Dekker
authors.forename: Sander
authors.initials: S
authors.lastname: Grefte
authors.forename: Tonnie
authors.initials: T
authors.lastname: Huijs
authors.forename: Gerdy B
authors.initials: GB
authors.lastname: ten Dam
authors.forename: Elly M M
authors.initials: EM
authors.lastname: Versteeg
authors.forename: Lieke C J
authors.initials: LC
authors.lastname: van den Berk
authors.forename: Bellinda A
authors.initials: BA
authors.lastname: Bladergroen
authors.forename: Toin H
authors.initials: TH
authors.lastname: van Kuppevelt
authors.forename: Carl G
authors.initials: CG
authors.lastname: Figdor
authors.forename: Ruurd
authors.initials: R
authors.lastname: Torensma
mesh_terms: D018949:Antigens, CD1 / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D006025:Glycosaminoglycans / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism / Q000502:physiology*; D037181:Lectins, C-Type / Q000096:biosynthesis; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D015854:Up-Regulation / Q000276:immunology*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D018949:Antigens, CD1; D018122:B7-1 Antigen; D015815:Cell Adhesion Molecules; D006025:Glycosaminoglycans; D015847:Interleukin-4; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C419393:CD1a antigen