| Project/Area Number |
16590749
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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 | Ehime University |
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Principal Investigator |
OGASAWARA Masahito Ehime University, School of Medicine, Associate professor, 医学部, 助教授 (00325367)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAUCHI Kohei Iwate medical University, School of Medicine, Associate professor, 医学部, 助教授 (20200579)
SAITO Shouichirou Gifu University, Basic verterinary Medicine, Associate professor, 応用生物学部, 助教授 (60325371)
MAEYAMA Kazutaka Ehime University, School of Medicine, Professor, 医学部, 教授 (00157158)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Acute Respiratory Distress Syndrome / Organic cation transporter / Knockout mice |
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| Research Abstract |
Acute respiratory distress syndrome (ARDS), which is caused by several etiology such as severe infection, shares common characteristics of pulmonary edema, acute alveolar injury and increased permeability of pulmonary capillary. Corticosteroids, anti-histamine agents and β-adrenergic receptor agonists have been considered as a potential treatment for ARDS. In some of the cases of ARDS, these therapies seem effective for improvement of mortality. From this evidence, histamine and catecholamines are thought to be involved in modification of pathology of ARDS. We investigated the role of organic cation transporters in LPS induced ARDS model using OCT-3 knockout(KO) mice. Organic cation transporters (OCTs) are expressed in extraneuronal tissues such as lung tissue and especially, OCT-2 and OCT-3 can transport histamine and catecholamines into cells and eliminate excess amount of histamine and catecholamine from the tissues. We tested survival rate in LPS induced endotoxemia model and found that the significant decrease in survival rate was shown in OCT3 KO mice. Furthermore, histamine content in spleen tissue of OCT-3 KO mice in LPS induced endotoxemia model was higher than that of wild type mice, suggesting that the higher content of histamine at the constitutional level have possibility to change Th1/Th2 balance through histamine receptors in T lymphocytes. Moreover, in this model of endotoxemia, inducible histamine production in macrophage would increase and inhibition of histamine clearance in microenvironment would participate in increase of histamine content due to OCT-3 deficiency.
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