| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Norihide Osaka University Graduate School of Medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
SAWA Yoshiki Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00243220)
SHIRAKURA Ryota Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
|
|---|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Research Abstract |
We have established the method to measure expressions of 65 different rat immune genes using fluorescent-based real time quantitative RT-PCR.We investigated the molecular mechanism of cardiac allograft vasculopathy (CAV) applying the technique established and PCR-DD on the rat heart retransplantation model of CAV and resulted in the three conclusions described below.
1. The short-term infiltration of alloreactive T cells into a graft is sufficient to cause CAV, nut not to complete acute rejection of rat cardiac allograft.
2. Importance of selective chemokine/receptor systems including IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2 was indicated in addition to the implication of cytokines produced by activated T cells (IFN-γ and Fas ligand), growth factors for vascular smooth muscle cells (PDGF-β, TGF-β) in the progression of CAV.
3. By PCR-DD, Immunogloblin kappa chain gene was shown to be preferentially expressed in cardiac allograft developing CAV, which was unexpected because previous literature described absence of B cells in cardiac allograft rejection both in animal model and clinical materials. In addition, B-cell chemo-attractant, BLC, its receptor CXCR5, and activation marker of B-cells, B7-2 gene expressions were also shown to be preferentially induced in the graft with CAV.Thus, it was suggested that syngeneic B cells actively infiltrate into the grafts and get activated in the course of chronic cardiac allograft rejection.
Using newly developed molecular techniques, we provided some new findings on the mechanism of cardiac allograft vasculopathy. This approach, together with more advanced molecular method such as RFDD analysis, should provide further insights in diagnosis and treatment of chronic cardiac allograft rejection.
|
