Characterization of beta-tricalcium phosphate as a novel immunomodulator

• Published in: International immunopharmacology Vol. 19; no. 1; pp. 45 - 51
• Main Authors: Tai, Sachiko, Cheng, Jin-Yan, Ishii, Hidee, Akimoto, Shingo, Satoh, Takatomo, Yamamoto, Kazumi, Nakajima, Takashi, Karaki, Sachiko, Suzuki, Emiko, Yamaguchi, Ken, Maruyama, Kouji
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2014
• Subjects: Adjuvant; Adjuvants, Immunologic - pharmacology; Animals; B7-2 Antigen - metabolism; Beta-tricalcium phosphate; Calcium Phosphates - pharmacology; Cancer immunotherapy; Cell Line; Cell Movement - drug effects; Chemokine CCL3 - metabolism; In vivo and in vitro immunostimulatory effects; Intercellular Adhesion Molecule-1 - metabolism; Macrophages - drug effects; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Monocytes - drug effects; Monocytes - physiology; Phagocytosis - drug effects; Spleen - cytology; Tumor Necrosis Factor-alpha - metabolism; In vivo and in vitro immunostimulatory effects; Adjuvant; Cancer immunotherapy; Beta-tricalcium phosphate
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.12.024

Calcium phosphate (CaP) ceramics including hydroxyapatite (HA) and beta-tricalcium phosphate (β-TCP) have been widely used for bone substitution in orthopedic, maxillofacial and dental surgery, as well as in tumor resections. CaP particles are also known to cause inflammatory responses, which are thought to be an unfavorable characteristic of prosthetic coating materials. On the other hand, the immunostimulatory effect of β-TCP induces an anti-tumor effect in xenograft tumor models in athymic mice. To date, in depth analysis of the biological effects of β-TCP has not been studied in mice.
In the present study, in vivo biological effects of β-TCP were investigated by subcutaneously injecting β-TCP particles into mice. This induced extensive migration of immune cells to the area surrounding the injection. In addition, we found that in vitro treatment with β-TCP in murine monocyte/macrophage cells (J774A.1) induced up-regulation of surface expression of CD86, and increased production of TNF-α, MIP-1α, and sICAM-1. Furthermore, conditioned medium from J774A.1 cells treated with β-TCP facilitated migration of murine splenocytes in a transwell migration assay. These findings clarify that β-TCP induces an immunostimulatory effect in mice, and suggest a potential for β-TCP as a novel adjuvant for cancer therapy.
•Subcutaneous injection of β-TCP in mice induced extensive migration of immune cells to the area surrounding β-TCP.•Co-culture with β-TCP induced maturation and production of TNF-α, MIP-1α, and sICAM-1 in mouse monocyte/macrophage cells.•Soluble factors from β-TCP-treated murine monocyte/macrophage cells facilitated migration of murine splenocytes.•These findings suggest the potential for β-TCP as a novel adjuvant for cancer immunotherapy.