RESUMO
Beta-tricalcium phosphate (ß-TCP) is widely used for bone substitution in clinical practice. Particles of calcium phosphate ceramics including ß-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 ß-TCP on the immune system could be utilized as an immunomodulator. Here, in vitro effects of ß-TCP on primary cultured murine dendritic cells (DCs) and macrophages were investigated. ß-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 ß-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 ß-TCP caused a prominent reduction in antigen uptake by DCs, and that conditioned medium from DCs treated with ß-TCP facilitated the migration of splenocytes in the transwell migration assay. Thus, ß-TCP induced phenotypical and functional maturation/activation of DCs and macrophages; these stimulating effects may contribute to the observed in vivo effect where ß-TCP induced extensive migration of immune cells. When compared to lipopolysaccharide (LPS), an authentic TLR ligand, the stimulatory effect of ß-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 ß-TCP against bone marrow-derived DCs and macrophages.
