| Project/Area Number |
17591001
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Saga University |
|---|
Principal Investigator |
FUKUDOME Kenji Saga University, Medicine, Associate Professor, 医学部, 助教授 (50284625)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KIMOTO Masao Saga University, Medicine, Professor, 医学部, 教授 (40153225)
TSUNEYOSHI Naoko Saga University, Medicine, Assistant Professor, 医学部, 助手 (80336114)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | protein C / endothelial cell / receptor / PAR / inflammation / トロンビン / 受容体 / モノクローナル抗体 |
|---|
| Research Abstract |
The endothelial cell protein C receptor (EPCR) is a type 1 transmembrane protein, which is capable of specific binding of protein C. We established monoclonal antibodies against the molecule, and demonstrated that EPCR was required for protein C activation under the physiological conditions. We also found that the binding function was not restricted to the zymogen form. Activated protein C (APC) bound to EPCR in the same manner as protein C. We detected EPCR expression in cancer cells. Complex formation of APC with EPCR on cancer cells may contribute to progression of cancer via catalytic activity to matrix metaroproteases. We also found the expression of the molecule on keratinocytes and microparticles. They may contribute to regulation of inflammation.
It has been demonstrated that APC was useful for therapy of endotoxin shock. Lipopolysaccharide (LPS) is the causative agent, and is known to induce various cell responses mainly mediated by the cell surface complex of Toll-like receptor 4 and MD-2. LPS needs to be processed by LPS-binding protein and CD14 to be recognized by the cell surface receptor complex. To analyze how APC/EPCR complex affects to the LPS-signaling pathway, we prepared recombinant proteins of these molecules. We will try to analyze molecular mechanisms of cross talking between blood coagulation and inflammation.
|
