title: Anti-P-selectin lectin-EGF domain monoclonal antibody inhibits the maturation of human immature dendritic cells.
abstract: Dendritic cells (DCs) are professional antigen-presenting cells with the ability to initiate primary T cell responses. While it is well known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DC maturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesion of P-, E-, and L-selectin, we demonstrate herein that selectins play important role in stimulating functional maturation of immature DCs. Immature DCs are generated from human cord blood CD34+ hematopoietic stem/progenitor cells that were cultured in the presence of stem cell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-beta1. When stimulated with tumor necrosis factor-alpha (TNF-alpha), immature DCs differentiated into mature DCs, producing increased levels of costimulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naïve T cells. Interestingly, in contrast to mature DCs derived from TNF-alpha-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for 7 days were completely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibited production of IL-12, and inability to activate naïve T cells in vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to be a valuable tool for the study of the molecular mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated autoimmunity.
authors.affiliation: Department of Nephrology, Rui Jin Hospital, Shanghai Second Medical University (SSMU), Shanghai 200025, China. zhoutong_cn@hotmail.com
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guizhi
authors.initials: G
authors.lastname: Sun
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dongqing
authors.initials: D
authors.lastname: Zhang
authors.forename: Yapeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Nan
authors.initials: N
authors.lastname: Chen
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019087:Selectins / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D019087:Selectins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D004815:Epidermal Growth Factor