1989 Fiscal Year Final Research Report Summary
Production and secretion of blood coagulation-fibrinolysis-platelet factors by human monocytes and megakaryocytes.
| Project/Area Number |
63480276
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Nagoya University School of Medicine |
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Principal Investigator |
SATIO Hidehiko Nagoya University School of Medicine, 医学部, 教授 (20153819)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAGUCHI Motohiro Nagoya University School of Medicine, 医学部, 医員
OGURA Michinori Nagoya University School of Medicine, 医学部, 医員
TAKAMATSU Junki Nagoya University School of Medicine, 医学部, 医員
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| Project Period (FY) |
1988 – 1989
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| Keywords | megakaryocytes / monocytes / beta-TG / thrombomodulin / cAMP / D-dimer / interleukins |
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| Research Abstract |
Recent studies suggest that leukocytes, platelets and vascular endothelial cells appear to participate actively in the process of thrombosis and hemostasis. We have investigated the production and secretion of blood coagulation-fibrinolysis-platelet factors by two unique human cell lines (MEG-01 and NOMO-1). MEG-01 and NOMO-1 represent good model for human megakaryocytes and monocytes, respectively, When MEG-01 cells were exposed to 10^<-7>M phorbol ester (TPA), they underwent morphological maturation and differentiation, and demonstrated enhanced production of fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). We have also demonstrated that intracellular ^cAMP-increasing agents enhanced the expression of thrombomodulin (TM) in MEG-01 cells. When MEG-01 cells were exposed to dibutyr _cAMP, forskolin or prostaglandin E_1 TM activity increased 3 15-fold over that of control cells.
Northern blot analysis showed time-dependent accumulation of TM mRNA. These results are significant in that it represents the first demonstration of up-regulation of TM. We have also observed similar phenomenon in human vascular endothelial cells. When NOMO-1 cells were exposed to TPA, lipid A or vitamin D3, they secreted increased amounts of interleukin 1, plasminogen activator and plasminogen activator inhibitor. Furthermore, FDP D-dimer was found to stimulate the production and secretion of interleukin 1, suggesting a new link between fibrinolysis and inflamatory reaction.
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