Anti-P-selectin lectin-EGF domain monoclonal antibody inhibits the maturation of human immature dendritic cells

查看全文 作　　者：Tong [1]Zhou;Yanyu [2]Zhang;Guizhi [1]Sun;Yumei [1]Zhang;Dongqing [3]Zhang;Yapeng [1]Zhao;Nan [1]Chen 机构地区：[1]Department of Nephrology, Rui Jin Hospital, Snanghai Second Medical University( SSMU ) , Shanghai 200025, China;[2]Joint Immunology Laboratory, Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai Institutes of Biological Sciences/SSMU, Chinese Academy of Sciences, shanghai 200025, China;[3]Shanghai Institute of Immunology, SSMU , Shanghai 200025, China 出　　处：《上海交通大学学报(医学版)》索引2006年第26卷第5期,共1页 摘　　要：Dendritic cells(DCs) are professinal antigen-presenting cells with the ability to initiate primary Tcell responses. While it iswell known that inflammatory stimuli induce the functional maturation of immature DCs, whether adhesion molecule selectins regulate DCmaturation is poorly understood. Using anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) that blocks the adhesionof 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 stemcell factor, Fms-like tyrosine-kinase-3 ligand, granulocyte-macrophage colony stimulating factor, and transform growth factor-β1. Whenstimulated with tumor necrosis factor-alpha(TNF-α), immature DCs differentiated into mature DCs, producing increased levels of costim-ulatory molecules and interleukin (IL)-12 and obtaining the ability to potently activate naive Tcells. Interestingly, in contrast to matureDCs derived from TNF-α-induced immature DC cultures without PsL-EGFmAb, immature DCs treated with PsL-EGFmAb for7 days werecompletely blocked their maturation, as evidenced by decreased expression of costimulatory molecules CD80, CD86, and CD83, inhibi-ted production of IL-12, and inability to activate naive Tcellsin vitro. Thus, blockade of selectins using PsL-EGFmAb will prove to bea valuable tool for the study of the molecuar mechanisms of DC maturation, as well as for the prevention and treatment of DC-mediated au-toimmunity. 关 键 词：抗P选择蛋白 植物凝血素 单克隆抗体 树状细胞