Role of Bone Marrow T Cells, Transendothelial Migratory T Cells and Anti-Endothelial Cell Antibodies in the Pathogenesis of Autoimmunity.

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09670489
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: Jichi Medical School
• Principal Investigator: KANO Shogo Jichi Medical School, Medicine, Professor, 医学部, 教授 (00049024)
• Co-Investigator(Kenkyū-buntansha): YOSHIO Taku Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (20221666) ; MASUYAMA Jun-ichi Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (20165731) ; OKAZAKI Hitoaki Jichi Medical School, Medicine, Ass.Professor, 医学部, 講師 (40285789)
• Project Period (FY): 1997 – 1998
• Keywords: systemic lupus erythematosus / apoptosis / ceramide / rheumatoid arthritis / transendothelial migration / anti-ribosomal P0 protein antibody

Research Abstract

1. MRL-lpr/lpr mouse has defect in apoptosis due to abnormal Fas gene and develops autoimmune diseases. Ceramide is an important mediator of intracellular signal transduction from Fas-Fas ligand interaction, and the cell membrane-permeable form C2-ceramide induced apoptosis in CD3+CD4-CD8-(DN) T cells from MIRL-lprllpr mice. FTY72O is a novel immunosuppressive agent resembling sphingosine in chemical structure. Oral administration of FTY72O as well as C2-ceramide reduced the number of DN T cells in lymph nodes and spleen of MRL-lpr/lpr mice, and significantly prolonged the survival at nine months.
2. A monoclonal antibody (4C8) was established, which inhibits the transendothelial migration of T cells without interfering their adhesion to endothelial cells. The 4C8 molecule also acts as the second signal of T cell activation.
3. Significantly elevated level of anti-endothelial cell antibody was found in SLE patients associated with pulmonary hypertension. One of the antigen recognized by anti-endothelial cell antibodies was identified as ribosomal P0 protein. Anti-ribosomal PG protein antibodies were found in sera from the patient with systemic lupus erythematosus(SLE). Positive anti-ribosomal P0 protein antibodies were associated with central nervous system involvement in SLE.A close temporal relationship of liver disease to anti-ribosomal P0 protein antibodies and central nervous system disease was also found in SLE patients.

Research Products

• [Publications] Yoshio T, Masuyama J, Minota S, Iwamoto M, Mimori A, Takeda A, Okazaki H, Kano S: "Correlation of serum IgG antibodies to recombinant PO fusion protein with IgG anntibodies to carboxyl-terminal 22 synthetic peptides and carboxyl-terminal 22 amino acid-deleted recombinant PO fusion protein in patients with systemic lupus crythematosus." Arthritis Rheum. 40(7). 1364-1365 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Horie S, Nakada K, Masuyama J-I, Yoshio T, Minota S, Wakabayashi Y, Hirose S and Kano S: "Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis." J Rheumatol. 24. 1517-1521 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoshio T., Masuyama, J., Kohda, N., Hirata, D., Sato, H., Iwamoto, M., Mimori, A., Takeda, A., Minota, S., and Kano, S.: "Association of Interleukin 6 Release from Endothelial Cells and Pulmonary Hypertension in SLE." J.Rheumatol.24. 489-495 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Hirata D, Hirai I, Iwamoto M, Yoshio T, Takeda A, Masuyama J-I, Mimori A, Kano S, Minota S: "Preferential binding with Escherichia coli hps60 of antibodies prevalent in sera from patients with rheumatoid arthritis." Clin Immunol Immunopathol. 82. 141-148 (1997)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Kamimura T, Mimori A, Takeda A, Masuyama J-I, Yoshio T, Okazaki H, Kano S, Minota S: "Acute acalculous cholecystitis in systemic lupus erythematosus : a case report and review of the literature." Lupus. 7. 361-363 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoshio T, Masuyama J-I, Minota S, Kaneko N, Iwamoto M, Okazaki H, Mimori A, Takeda A, Kano S: "A close temporal relationship of liver disease to antiribosomal PO protein antibodie〓 and central nervous system disease in patients with systemic lupus erythematosus." Circulation. 25. 681-688 (1998)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Yoshio T,Masuyama J-I,Kohda N,Hirata D,Sato H,Iwamoto M,Mimori A,Takeda A,Minota S and Kano S: "Association of interleukin 6 release from endothelial cells and pulmonary hypertension in SLE." J Rheumatol. 24. 489-495 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Horie S,Nakada K,Masuyama J-I,Yoshio T,Minota S,Wakabayashi Y,Hirose S and Kano S: "Detection of large macrophage colony forming cells in the peripheral blood of patients with rheumatoid arthritis." J Rheumatol. 24. 1517-1521 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yoshio T,Masuyama J-I,Minota S,Iwamoto M,Mimori A,Takeda A,Okazaki H,Kano S: "Correlation of serum IgG antibodies to recombinant P0 fusion protein with IgG antibodies to carboxyl-terminal 22 synthetic peptides and carboxyl-terminal 22 amino acid-deleted recombinant P0 fusion protein in patients with systemic lupus erythematosus." Arthritis Rheum. 40. 1364-1365 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Hirata D,Hirai I,Iwamoto M,Yoshio T,Takeda A,Masuyama J-I,Mimori A,Kano S and Minota S: "Preferential binding with Escherichia coli hps60 of antibodies prevalent in sera from patients with rheumatoid arthritis." Clin Immunol Immunopathol. 82. 141-148 (1997)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Kamimura T,Mimori A,Takeda A,Masuyama J-I,Yoshio T,Okazaki H,Kano S and Minota S: "Acute acalculous cholecystitis in systemic lupus erythematosus : a case report and review of the literature." Lupus. 7. 361-363 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Yoshio T,Masuyama J-I,Minota S,Kaneko N,Iwamoto M,Okazaki H,Mimori A,Takeda A and Kano S: "A close temporal relationship of liver disease to antiribosomal P0 protein antibodies and central nervous system disease in patients with systemic lupus erythematosus." J Rheumatol. 25. 681-688 (1998)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Funayama H,Ikeda U,Takahashi M,Sakata Y,Kitagawa S,Takahashi Y,Masuyama J-I,Furukawa Y,Miura Y,Kano S,Matsuda M and Shimada K: "Human monocyte-endothelial cell interaction induces platelet-derived growth factor expression." Cardiovasc Res. 37. 216-224 (1998)
  • Description: 「研究成果報告書概要(欧文)」より