title: Effects of beta-tricalcium phosphate particles on primary cultured murine dendritic cells and macrophages.
abstract: Beta-tricalcium phosphate (β-TCP) is widely used for bone substitution in clinical practice. Particles of calcium phosphate ceramics including β-TCP act as an inflammation mediators, which is an unfavorable characteristic for a bone substituent or a prosthetic coating material. It is thought that the stimulatory effect of β-TCP on the immune system could be utilized as an immunomodulator. Here, in vitro effects of β-TCP on primary cultured murine dendritic cells (DCs) and macrophages were investigated. β-TCP particles enhanced expression of costimulatory surface molecules, including CD86, CD80, and CD40 in DCs, CD86 in macrophages, and MHC class II and class I molecules in DCs. DEC205 and CCR7 were up-regulated in β-TCP-treated DCs. Production of cytokines and chemokines, including CCL2, CCL3, CXCL2, and M-CSF, significantly increased in DCs; CCL2, CCL3, CCL4, CCL5, CXCL2, and IL-11ra were up-regulated in macrophages. The results of the functional assays revealed that β-TCP caused a prominent reduction in antigen uptake by DCs, and that conditioned medium from DCs treated with β-TCP facilitated the migration of splenocytes in the transwell migration assay. Thus, β-TCP induced phenotypical and functional maturation/activation of DCs and macrophages; these stimulating effects may contribute to the observed in vivo effect where β-TCP induced extensive migration of immune cells. When compared to lipopolysaccharide (LPS), an authentic TLR ligand, the stimulatory effect of β-TCP on the immune systems is mild to moderate; however, it may have some advantages as a novel immunomodulator. This is the first report on the direct in vitro effects of β-TCP against bone marrow-derived DCs and macrophages.
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan; Division of Life Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tai
authors.affiliation: Advanced Analysis Technology Department, Corporate R&D Center, Olympus Corporation, Tokyo, Japan.
authors.forename: Jin-Yan
authors.initials: JY
authors.lastname: Cheng
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Hidee
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Kasumi
authors.initials: K
authors.lastname: Shimono
authors.affiliation: Regional Resource Division, Shizuoka Cancer Center Research Institute, Shizuoka, Japan.
authors.forename: Vincent
authors.initials: V
authors.lastname: Zangiacomi
authors.affiliation: Advanced Analysis Technology Department, Corporate R&D Center, Olympus Corporation, Tokyo, Japan.
authors.forename: Takatomo
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Laboratory of Medicinal Microbiology, Yokohama College of Pharmacy, Kanagawa, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Hosono
authors.affiliation: Division of Life Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Shizuoka Cancer Center Hospital and Research Institute, Shizuoka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Experimental Animal Facility, Shizuoka Cancer Center Research Institute, Shizuoka, Japan. Electronic address: k.maruyama@scchr.jp.
authors.forename: Kouji
authors.initials: K
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000276:immunology; D002130:Calcium Phosphates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D061251:Primary Cell Culture
chemical_list: D015703:Antigens, CD; D002130:Calcium Phosphates; D016207:Cytokines; D007155:Immunologic Factors; D018836:Inflammation Mediators; C485817:beta-tricalcium phosphate
keywords: Beta-tricalcium phosphate; Dendritic cells; Immunomodulator; Macrophages; Primary culture