| Project/Area Number |
05454202
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Immunology
|
|---|
| Research Institution | TOHOKU UNIVERSITY |
|---|
Principal Investigator |
KUMAGAI Katsuo Tohoku Univ. Dentistry ant Prof., 歯学部, 教授 (00005018)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HANAUMI Kiyoshi Tohoku Univ. Dentistry Assist Prof., 歯学部, 助手 (50005063)
RIKIISHI Hidemi Tohoku Univ. Dentistry Assist ant Prof., 歯学部, 助手 (70091767)
SUGAWARA Shunji Tohoku Univ. Dentistry Assist ant Prof., 歯学部, 助手 (10241639)
|
|---|
| Project Period (FY) |
1993 – 1994
|
| Project Status |
Completed (Fiscal Year 1994)
|
| Budget Amount *help |
¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1993: ¥3,700,000 (Direct Cost: ¥3,700,000)
|
|---|
| Keywords | MRL / 1pr mice / IL-6 / ICAM-1 / Liver / Autoimmune disease / MRL-1prマウス / MRL-lpr / lprマウス |
|---|
| Research Abstract |
MRL/1pr mice, which are a model of SLE and rheumatoid arthritis in humans, develop profound lymphadenopathy resulting from the accumulation of CD3^+ 4^- 8^- double-negative (DN) alpha beta T cells in peripheral lymphoid tissues. We previously indicated that these DN alpha beta T cells preferentially proliferate in the liver and migrate to the periphery. In this study, we analyzed whether any kind of cytokine was produced by hepatic mononuclear cells (MNC) in MRL/1pr mice. The evidence obtained indicates that interleukin 6 (IL-6) was vigorously produced by hepatic MNC in diseased MRL/1pr mice under unstimulated conditions. MNC in the spleen of these mice produced small amounts of IL-6, while those in the lymph nodes did not produce any appreciable amounts of IL-6. These activities of hepatic MNC in diseased MRL/1pr mice were almost completely neutralized by anti-mouse IL-6 monoclonal antibody (mAb).
On the other hand, immunohistochemical staining of light-and electron-microscopic analyzes revealed that the intracellular cell abhesion molecule 1 (ICAM-1) was expressed on the hepatic sinusoidal endothelial cells of diseased MRL/1pr mice. Moreover, ICAM-1 was newly induced in the hepatic sinusoids of control C3H/He mice by an intravenous injection of 50 units of recombinant mouse IL-6. These data suggest that ICAM-1 expressed on the hepatic sinusoidal endothelial cells in MRL/1pr mice is induced by IL-6, which is produced by hepatic MNC,and that such ICAM-1 may be responsible for the saturation of inflammatory cells and the proliferation of lymphocytes in the liver of MRL/1pr mice.
|
