COMPLEMENT RECEPTOR EXPRESSION AND FUNCTION ON NORMAL AND LJP NEUTROPHILS

局限性青少年牙周炎(LJP)是一种青少年疾病 以严重的牙槽骨丢失为特征，主要局限于 第一颗磨牙和门牙。这些细胞的免疫学评价 患者已发现一种固有的中性粒细胞趋化缺陷 在大约70%的研究患者中。趋化作用 LJP中性粒细胞缺陷似乎与减少有关 趋化物质的膜受体数量。 然而，趋化缺陷的分子基础 LJP中性粒细胞的特征尚未定义。 中性粒细胞是一种动态细胞，能够改变其代谢。 对不同的外界刺激作出反应的性格。暴露于 这些细胞对趋化因子的趋化作用增强了其C3的表达 感受器。在随后暴露于结缔组织时 纤维连接蛋白、C3受体等蛋白质被“激活” 这样它们就能调节C3包裹颗粒的摄取。是否 趋化素受体数量减少的存在限制了 LJP中性粒细胞增加C3表达的能力 趋化因子刺激后的受体或 这些受体在纤维连接蛋白之后被激活 暴露问题尚未得到解决。 长期以来，人们一直认为外周血中性粒细胞 同质的。然而，最近的研究表明，这些细胞 在功能上相当不同。此外，出现了 抗原性不同的中性粒细胞亚群 用单抗和流式细胞仪进行演示 技巧。已有研究表明，中性粒细胞的异质性 可能与某些病理状态有关。一个主要的 因此，拟议研究的重点将是利用流量 细胞计量学方法在评估功能性损伤程度中的应用 LJP中性粒细胞表达的异质性 第三和第五生物活性片段的受体 补语的成分。利用这一事实， 与终末分化的中性粒细胞不同，未成熟的中性粒细胞 表达C3d的膜受体(称为CR2受体) 建议研究抗CR2的单抗与 LJP中性粒细胞的流式细胞术和 使用放射性标记抗体的常规结合试验。 此外，将利用流式细胞术方法评估C3 趋化素组和未处理组的受体表达 中性粒细胞。另一个具体目标将是定义容量 趋化因子对纤维连接蛋白激活C3受体的影响 LJP中性粒细胞，由C3包被的吞噬作用测定 红血球。拟议研究的结果将提供 有关性质和功能的基本信息 趋化因子低反应性的后果 LJP中性粒细胞的特征。

Localized juvenile periodontitis (LJP) is an adolescent disease characterized by severe alveolar bone loss confined largely to the first molars and incisors. Immunologic evaluation of these patients has revealed an intrinsic neutrophil chemotactic defect in approximately 70% of the patients studied. The chemotactic defect of LJP neutrophils appears to be correlated with reduced numbers of membrane receptors for chemotactic substances. Nevertheless, a molecular basis of the chemotactic defect characteristic of LJP neutrophils has not been defined. Neutrophils are dynamic cells capable of altering their metabolic disposition in response to diverse external stimuli. Exposure of these cells to chemotaxins augments their expression of C3 receptors. Upon subsequent exposure to connective tissue proteins such as fibronectin, C3 receptors become "activated" such that they mediate ingestion of C3-coated particles. Whether the presence of reduced numbers of chemotaxin receptors limits the capacity of LJP neutrophils to increase expression of C3 receptors following chemotaxin stimulation or the capacity of these receptors to become activated subsequent to fibronectin exposure has not been addressed. It has long been assumed that peripheral blood neutrophils are homogeneous. Recent studies indicate, however, that these cells are functionally quite heterogeneous. Moreover, the presence of antigenically distinct subpopulations of neutrophils has been demonstrated using monoclonal antibodies and flow cytometric techniques. It has been suggested that neutrophil heterogeneity may have implications in certain pathologic states. A primary focus of the proposed studies will be, therefore, to utilize flow cytometric methods in assessing the extent of functional heterogeneity of LJP neutrophils with respect to expression of receptors for biologically active fragments of the third and fifth components of complement. Taking advantage of the fact that, unlike terminally differentiated neutrophils, immature neutrophils express membrane receptors for C3d (termed CR2 receptors), we propose to study binding of a monoclonal anti-CR2 antibody to LJP neutrophils using both flow cytometric methods and conventional binding assays employing radiolabeled antibody. Further, flow cytometric methods will be utilized to assess C3 receptor expression on untreated and chemotaxin-treated neutrophils. A further specific aim will be to define the capacity of fibronectin to activate C3 receptors on chemotaxin-treated LJP neutrophils, as determined by phagocytosis of C3-coated erythrocytes. The results of the proposed studies will provide fundamental information regarding the nature and functional consequences of chemotactic factor hyporesponsiveness characteristics of LJP neutrophils.