論文 - 詳細
| RRC ID | 1917 |
|---|---|
| 著者 | Nagayoshi R, Nagai T, Matsushita K, Sato K, Sunahara N, Matsuda T, Nakamura T, Komiya S, Onda M, Matsuyama T. |
| タイトル | Effectiveness of anti-folate receptor beta antibody conjugated with truncated Pseudomonas exotoxin in the targeting of rheumatoid arthritis synovial macrophages. |
| ジャーナル | Arthritis Rheum |
| Abstract |
OBJECTIVE:To define the distribution of folate receptor beta (FRbeta)-expressing cells in various tissues, including rheumatoid arthritis (RA) synovial tissues, and to verify the effects of an immunotoxin composed of an anti-FRbeta monoclonal antibody (mAb) and truncated Pseudomonas exotoxin A (PEA) on apoptosis and tumor necrosis factor alpha (TNFalpha) production by adherent synovial mononuclear cells from RA patients. METHODS:Anti-FRbeta mAb were produced by immunizing mice with FRbeta-transfected murine pre-B cells. The distribution of the FRbeta antigen was examined by immunohistochemical analysis using anti-FRbeta mAb and macrophage-specific anti-CD163 mAb. Anti-FRbeta mAb was chemically crosslinked with truncated PEA. FRbeta-expressing macrophages were produced by the transfection of adenovirus vector containing the FRbeta gene. Apoptotic cells were detected by staining with propidium iodide. TNFalpha was measured by enzyme-linked immunosorbent assay. RESULTS:FRbeta-expressing cells were not present in peripheral blood leukocytes and their activated cells. In all of the tissues examined, most FRbeta-expressing cells were CD163+. The immunotoxin significantly induced the apoptosis of FRbeta-transfected macrophages and adherent RA synovial mononuclear cells and inhibited TNFalpha production by adherent RA synovial mononuclear cells. CONCLUSION:We demonstrated the limited distribution of FRbeta-expressing cells in various tissues. The immunotoxin targeting FRbeta-expressing cells will provide a therapeutic tool for rheumatoid synovitis. |
| 巻・号 | 52(9) |
| ページ | 2666-75 |
| 公開日 | 2005-9-1 |
| DOI | 10.1002/art.21228 |
| PMID | 16142741 |
| MeSH | ADP Ribose Transferases / immunology* ADP Ribose Transferases / metabolism Animals Antibodies, Monoclonal / immunology Antibodies, Monoclonal / pharmacology* Antibody-Dependent Cell Cytotoxicity / drug effects Antigens, CD / metabolism Antigens, Differentiation, Myelomonocytic / metabolism Apoptosis / drug effects Arthritis, Rheumatoid* / drug therapy Bacterial Toxins / immunology* Bacterial Toxins / metabolism Carrier Proteins / immunology* Carrier Proteins / metabolism Dose-Response Relationship, Immunologic Exotoxins / immunology* Exotoxins / metabolism Folate Receptors, GPI-Anchored Humans Immunotoxins / immunology Immunotoxins / pharmacology* Macrophage Activation Macrophages / drug effects* Macrophages / metabolism Macrophages / pathology Mice Mice, Inbred BALB C Receptors, Cell Surface / immunology* Receptors, Cell Surface / metabolism Synovial Membrane / drug effects* Synovial Membrane / metabolism Synovial Membrane / pathology Tumor Necrosis Factor-alpha / metabolism Virulence Factors / immunology* Virulence Factors / metabolism |
| 引用数 | 51 |
| WOS 分野 | RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |