MONOCYTE-SPECIFIC CHEMOATTRACTANT FROM HUMAN PMN

中性粒细胞（Pmns）和单核细胞的迁移是其中之一。 炎症的基本事件。 这些细胞与 消除有害微生物、毒素和变性蛋白质， 对外来抗原的免疫反应。 PMNs是主要的细胞 在急性炎症阶段，而单核细胞被发现在 慢性期 介导第二波炎症的刺激 导致了 单核细胞进入一个区域尚未 被阐明。 这项研究提出的假设是， 单核细胞的流入部分是由于化学引诱物的释放 来自中性粒细胞本身，或者在中性粒细胞死亡后， 或在脱粒之后。 这个假设的正确性 将 由以下具体目标决定。 目标1：证明 一种天然存在的人Pmns阳离子颗粒蛋白，Mr 37000 D （CAP 37）具有对人单核细胞特异性的有效趋化活性， 通过改良的Boyden室技术测量，并问什么 CAP 37在人单核细胞中诱导的其它反应。 目标2：确定 CAP 37的氨基酸序列及其克隆和序列分析 结构基因，以确定负责趋化的结构域 活动 目的3，询问单核细胞是否具有特异性受体， 介导趋化性。 用放射性标记的蛋白质，我们将尝试检测 并测量人CAP 37上的可饱和和特异性结合位点， 单核细胞 目的4，评价CAP 37作为单核细胞的作用， 体内特异性化学引诱物，并询问CAP 37可能 在体内对单核细胞/巨噬细胞施加。 溶酶体的释放 酶、IL-1、肿瘤坏死因子、超氧化物生成，以及 La（II类MHC蛋白）的表达将用标准品测定。 测定。 相信通过这些调查，CAP 37将成为 证实可引起单核细胞迁移并调节其他功能 在体内，它对单核细胞和巨噬细胞的活性的影响， 将确定炎症部位。

The emigration of neutrophils (Pmns) and monocytes is one of the fundamental events in inflammation. These cells are intimately involved in the elimination of harmful microbes, toxins, and denatured proteins and in the immune reaction to foreign antigens. Pmns are the predominant cell in the acute inflammatory stage, whereas monocytes are found in the chronic stage. The stimulus that mediates the second wave of inflammation resulting in the migration of monocytes into an area has not yet been elucidated. The hypothesis proposed in this study is that this influx of monocytes is in part due to the liberation of a chemoattractant from the neutrophil itself, either following the death of the neutrophil or subsequent to degranulation. The validity of this hypothesis will be determined by the following specific aims. Aim 1, to demonstrate that a naturally occurring cationic granule protein of human Pmns of Mr 37000D (CAP37) has potent chemotactic activity specific for human monocytes, as measured by the modified Boyden chamber technique, and to ask what other responses CAP 37 induces in human monocytes. Aim 2, to determine the amino acid sequence of CAP 37 and the cloning and sequencing of its structural gene so as to define the domains responsible for chemotactic activity. Aim 3, to ask if monocytes have specific receptors that mediate chemotaxis. With radiolabeled proteins we will attempt to detect and measure the saturable and specific binding sites for CAP37 on human monocytes. Aim 4, to evaluate the role of CAP37 as a monocyte- specific chemoattractant in vivo and to ask what other responses CAP37 may exert on monocytes/macrophages in vivo. The release of lysosomal enzymes, IL-1, tumor necrosis factor, superoxide production, and expression of La (class II MHC protein) will be determined with standard assays. It is believed that through these investigations CAP37 will be demonstrated to cause migration of monocytes and modulate other functions in vivo, and that its effects on the activity of monocytes and macrophages at the sites of inflammation will be determined.