title: Mannan-binding lectin at supraphysiological concentrations inhibits differentiation of dendritic cells from human CD14+ monocytes.
abstract: Mannan-binding lectin (MBL), a circulating C-type lectin, is an important member of the defense collagen family. It exhibits a high potential for recognizing broad categories of pathogen-associated molecular patterns and initiating complement cascade responses. DCs are well-known specialist antigen-presenting cells that significantly trigger specific T cell-mediated immune responses. In our previous study, it was observed that high concentrations of MBL significantly attenuate LPS-induced maturation of monocyte-derived DCs (MoDCs). In the current study, it was postulated that MBL at similar supraphysiological concentrations would affect early differentiation of MoDCs in some way. CD14(+) monocytes from human peripheral blood mononuclear cells were cultured with granulocyte-macrophage colony-stimulating factor and IL-4 in the presence or absence of physiological (1 µg/mL) and supraphysiological concentrations (20 µg/mL) of MBL protein, respectively. Phenotypic analysis indicated that the differentiated DCs incubated with high concentrations of MBL expressed MHC class II and costimulatory molecules (e.g., CD80 and CD40) more weakly than did control groups. The secretion of IL-10 and IL-6 increased markedly, whereas their mixed lymphocyte reaction-stimulating capacity decreased. Members of the signal transducer and activator of transcription family were also found to be differentially regulated. Thus, beyond the role of MBL as an opsonin, our data reveal a possible inhibitory effect of MBL at high concentrations in monocyte-DC transition, which probably provides one way of regulating adaptive immune responses by strict regulation of DCs, making MBL a better prospect for controlling relevant pathological events such as autoimmune diseases.
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Hui-Jie
authors.initials: HJ
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Da-Ming
authors.initials: DM
authors.lastname: Zuo
authors.affiliation: Guangzhou General Hospital of Guangzhou Military Command, Liuhua Road 111, Guangzhou, Guangdong, China.
authors.forename: Gui-Qiu
authors.initials: GQ
authors.lastname: Shan
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Tian-Yu
authors.initials: TY
authors.lastname: Xu
authors.affiliation: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou Avenue North 1838, Guangdong, China.
authors.forename: Zheng-Liang
authors.initials: ZL
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis* / Q000276:immunology; D037601:Mannose-Binding Lectin / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010641:Phenotype; D011485:Protein Binding; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; C508609:IL10 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D037601:Mannose-Binding Lectin; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: concentration; dendritic cell differentiation; mannan-binding lectin; monocyte