| Project/Area Number |
16390108
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kumamoto University |
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Principal Investigator |
TAKEYA Motohiro Kumamoto University, Graduate School of Medical Sciences, Professor (90155052)
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| Co-Investigator(Kenkyū-buntansha) |
SAKASHITA Naomi Kumamoto University, Graduate School of Medical Sciences, Associate Professor (90284752)
KAIKITA Koichi Kumamoto University, Graduate School of Medical Sciences, Assistant professor (30346978)
寺崎 泰弘 熊本大学, 大学院・医学薬学研究部, 助手 (50332870)
吉松 美佳 熊本大学, 大学院・医学薬学研究部, 助手 (50372785)
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| Project Period (FY) |
2004 – 2007
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2006: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2004: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | macrophages / class A scavenger receptor I, and II (CD204) / hemoglobin-scavenger receptor (CD163) / scavenger recepter family / immunohistochemistry / alternative activation / CD204-deficient mice / animal model / SR-AI,II(CD204) / モノクローナル抗体 / 樹状細胞 / マクロファージ亜群 / マクロファージ活性化 / マクロファージ分化 / 免疫組織化学 / パターン認識受容体 |
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| Research Abstract |
Scavenger receptors possess wide-ranged ligand-binding specificities and are considered to be one of the pattern recognition receptors that play important roles in host defence. Among such receptors, CD204 (Class A scavenger receptor Type I and II) and CD163 (hemoglobin scavenger receptor) are expressed exclusively on macrophages and considered to be a good marker for macrophages in histopathology. Using self-made antibodies, we have shown that CD204 and CD163 are positive for resident macrophages and a population of inflammatory macrophages in paraffin sections. In granulomatous diseases such as tuberculosis and sarcoidosis, infiltrated macropages surrounding the granulomas were positive for CD204 and CD163, however multinucleated giant cells were negative or only weakly labeled. Since CD204 and CD163 are induced in alternatively activated macrophages, these antibodies are considered to be valuable tools to label such macrophage subpopulation in hitopathological specimens.
In animal models of acute myocardial infarction and high-dose oxygen-induced lung injury, CD204-deficient mice showed exacerbation of disease process in both models. In myocardial infarction model, CD204-deficiency showed increased ratio of cardiac rupture with increased expression of TNF- a and enhanced activation of matrix metalloproteinases (MMP). In lung injury model, CD204-deficiency also showed higher expression of TNF- a and increased MMP activity. These results indicate that CD204-positive macrophages regulate inflammatory process by suppressing the excessive inflammatory responses.
In the future experiments, such anti-inflammatory alternatively activated macrophages will be evaluated in various human diseases using self-made antibodies against CD204 and CD 163.
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