2007 Fiscal Year Final Research Report Summary
Therapeutic effect of combined protein C pathway factors on acutelung injury
| Project/Area Number |
18590846
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Mie University |
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Principal Investigator |
TAGUCHI Osamu Mie University, Hospital, Lecturer (90197244)
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| Co-Investigator(Kenkyū-buntansha) |
GABAZZA Esteban Mie University, Graduate School of Medicine, Professor (00293770)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Acute lung iniury / Combined therapy / Protein S / Protein C pathway / Cytokines / Sepsis / Activated protein C / Coagulation system |
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| Research Abstract |
Background: Protein S (PS) and activated protein C (APC) have anticoagulant and anti-inflammatory activities. PS may exert anticoagulant activity by favoring the anticoagulant activity of APC and/or by directly inhibiting the prothrombinase complex. The role of PS and the combination of PS and APC on acute lung injury have not been as yet appraised.
Objective : The aim of this present study was to evaluate the effect of PS and APC plus PS on acute lung injury in the mouse.
Methods : Acute lung injury was induced in C57/BL6 mice by intratracheal instillation of lipopolysaccharide(LPS)(5mg/kg). Mice treated with saline served as controls. To evaluate the therapeutic effect of PS and APC plus PS, the animals were treated with PS alone, a combination of PS and APC or saline by intraperitoneal injection one hour before LPS instillation. These animals were sacrificed 24 hours after LPS injection and sampling of bronchoalveolar lavage fluid and lung tissue were performed. The in vitro effect of PS on secretion of inflammatory cytokines from alveolar epithelial cells was also assessed.
Results : The total cell count and the bronchoalveolar lavage fluid level of total protein, interleukin-6 and monocyte chemoattractant protein-1 were significantly increased in LPS-treated mice compared with controls. Mice with acute lung injury treated with PS and combined therapy of PS plus APC had significantly decreased concentration of interleukin-6 and monocyte chemoattractant protein-1 in bronchoalveolar lavage fluid as compared to untreated animals. Treatment with protein C pathway factors also improved lung pathological changes. PS alone significantly abated the expression of inflammatory cytokines from alveolar epithelial cells.
Conclusions : These results suggest that combined administration of protein C pathway factors may be a potential therapeutic strategy for the therapy of acute lung injury.
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Yamaguchi, A, Gabazza, EC, Takei, Y, Yano, Y, Fujimoto, H, D'Alessandro-Gabazza, CN, Murakami, E, Kobayashi, T, Takagi, T, Maruyama, J, Suzuki, K, Taguchi, O
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Fujimoto, H, D'Alessandro-Gabazza, CN, Palanki, MS, Erdman, PE, Takagi, T, Gabazza, EC, Bruno, NE, Yano, Y, Hayashi, T, Tamaki, S, Sumida, Y, Adachi, Y, Suzuki, K, Taguchi, O
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[Journal Article] Deficiency of tenascin C attenuates allergen-induced bronchial asthma in the mouse2006
Author(s)
Nakahara, H, Gabazza, EC, Fujimoto, H, Nishii, Y, D'Alessandro-Gabazza, CN, Bruno, NE, Takagi, T, Hayashi, T, Maruyama, J, Maruyama, K, Imanaka-Yoshida, K, Suzuki, K, Yoshida, T, Adachi, Y, Taguchi, O
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Journal Title
Eur J Immunol 36
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[Journal Article] Protective role of protein C inhibitor in monocrotaline-induced pulmonary hypertension2006
Author(s)
Nishii, Y, Gabazza, EC, Fujimoto, H, Nakahara, H, Takagi T, Bruno, N, D'Alessandro-Gabazza, CN, Maruyama, Maruyama, K, Hayashi, T, Adachi, Y, Suzuki, K, Taguchi, O
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Journal Title
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[Presentation] Role of NF-kappaB p50 in bleomycin-induced pulmonary fibrosis2007
Author(s)
Takagi, T, Gabazza, EC, Fujimoto, H, Maruyama, T, Nishii, Nakahara, H, D'Alessandro-Gabazza, CN, Kobayashi, H, Taguchi, O
Organizer
European Respiratory Society International Congress
Place of Presentation
Stockholm, Sweden
Year and Date
2007-09-17
Description
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[Presentation] Role of Thrombin in Interleukin-5 Secretion from Basophils2007
Author(s)
Yamaguchi, A, Gabazza, EC, Takagi, T, Nakahara, H, H., Fujimoto, H, Kobayashi, T, Kobayashi, H, D'Alessandro-Gabazza, CN, Taguchi, O
Organizer
American Thoracic Society International Congress
Place of Presentation
San Francisco, California, USA
Year and Date
2007-05-22
Description
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