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Application of CD204 (scavenger receptor) to histopathological diagnosis and production of new anti-macrophage antibodies

CD204（清道夫受体）在组织病理学诊断和新型抗巨噬细胞抗体生产中的应用

基本信息

批准号：
16390108
负责人：
TAKEYA Motohiro
金额：
$ 8.77万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2007
项目状态：
已结题

项目摘要

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.

清道夫受体具有广泛的配体结合特异性，被认为是在宿主防御中发挥重要作用的模式识别受体之一。在这些受体中，CD204(A类清道夫受体I和II型)和CD163(血红蛋白清道夫受体)仅在巨噬细胞上表达，被认为是组织病理学中很好的巨噬细胞标志物。使用自制的抗体，我们发现CD204和CD163在石蜡切片中的常驻巨噬细胞和炎性巨噬细胞群中呈阳性。在结核、结节病等肉芽肿性疾病中，肉芽肿周围浸润性巨细胞CD204和CD163阳性，多核巨细胞阴性或仅弱标记。由于CD204和CD163在交替激活的巨噬细胞中被诱导，这些抗体被认为是在组织病理学标本中标记这种巨噬细胞亚群的有价值的工具。在急性心肌梗死和大剂量氧致肺损伤的动物模型中，CD204缺乏的小鼠在这两种模型中都表现出疾病过程的恶化。在心肌梗死模型中，CD204缺陷表现为心脏破裂的发生率增加，并伴随着肿瘤坏死因子-α的表达增加和基质金属蛋白酶的激活。在肺损伤模型中，CD204缺陷组也表现出较高的肿瘤坏死因子-α表达和基质金属蛋白酶活性。这些结果表明，CD204阳性的巨噬细胞通过抑制过度的炎症反应来调节炎症过程。在未来的实验中，这种抗炎或激活的巨噬细胞将利用自制的CD204和CD163抗体在各种人类疾病中进行评估。