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 特征是严重的牙槽骨丢失，主要局限于 第一臼齿和门牙 免疫学评价这些 患者发现了一种内在的中性粒细胞趋化缺陷 在大约70%的患者中。 趋化 LJP中性粒细胞的缺陷似乎与减少 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确定。 中性粒细胞是动态细胞，能够改变其代谢 对各种外部刺激的反应。 暴露 这些细胞对趋化因子的依赖增强了它们C3的表达， 受体。 随后暴露于结缔组织后 纤维连接蛋白、C3受体等蛋白质被“激活”， 使得它们介导C3包覆的颗粒的摄入。 是否 趋化因子受体数量减少限制了 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 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是 同质的 最近的研究表明，这些细胞 在功能上是非常异质的。 此外， 嗜中性粒细胞的抗原性不同的亚群一直是 使用单克隆抗体和流式细胞术证明 技术. 有人认为，中性粒细胞异质性 可能在某些病理状态下有影响。 主 因此，拟议研究的重点将是利用流量 细胞计数法在评估功能性 LJP中性粒细胞表达的异质性 第三和第五的生物活性片段的受体 补充的成分。 利用这个事实， 与终末分化的中性粒细胞不同， 表达C3d的膜受体（称为CR2受体），我们 建议研究单克隆抗CR2抗体与 LJP中性粒细胞使用两种流式细胞术方法， 使用放射性标记抗体的常规结合测定。 此外，将使用流式细胞术方法评估C3 未处理和趋化因子处理的受体表达 中性粒细胞 另一个具体目标将是确定 纤连蛋白激活趋化因子处理的C3受体 LJP中性粒细胞，通过吞噬C3包被的 红细胞 拟议研究的结果将提供 关于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.