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

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起重要作用的模式识别受体之一。在这些受体中，CD 204（A类清道夫受体I型和II型）和CD 163（血红蛋白清道夫受体）仅在巨噬细胞上表达，并被认为是组织病理学中巨噬细胞的良好标志物。使用自制的抗体，我们已经表明，CD 204和CD 163是阳性的居民巨噬细胞和一个群体的炎性巨噬细胞在石蜡切片。在肉芽肿性疾病如结核病和结节病中，肉芽肿周围浸润的巨噬细胞CD 204和CD 163阳性，而多核巨细胞阴性或仅弱标记。由于CD 204和CD 163在交替激活的巨噬细胞中被诱导，这些抗体被认为是标记hitopathological samples.In急性心肌梗死和高剂量氧诱导的肺损伤的动物模型中的巨噬细胞亚群的有价值的工具，CD 204缺陷的小鼠在两种模型中显示疾病过程的加重。在心肌梗死模型中，CD 204缺陷导致心脏破裂发生率增加，TNF-α表达增加，基质金属蛋白酶（MMP）活化增强。在肺损伤模型中，CD 204缺陷也显示TNF-α表达增加和MMP活性增加。这些结果表明，CD 204阳性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，将使用自制的抗CD 204和CD 163的抗体来评估这种抗炎性的交替激活的巨噬细胞在各种人类疾病中的作用。

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.