ROLE OF GINGIVAL FLUID POLYAMINES IN PMN MODULATION

中性粒细胞（PMN）是宿主防御的重要组成部分， 牙周病和其他细菌感染。 PMN功能 通过配体与表面受体的结合来调节，这是一种发生- 磷酸肌醇水解产物和瞬时增加， 胞浆Ca ~（2+）。 这些细胞内信号相互合作， 动员蛋白激酶C（PKC）并启动许多必需的PMN活性， 关系的 最近的证据表明，Ca 2+信号传导显着 多胺改变，这是普遍存在于牙龈液， 牙周袋发炎 基于这些证据，我们假设 牙龈液多胺可以显著延长 受体操纵的Ca 2+动员和Ca 2+依赖的PKC动员， 作用，从而调节许多重要的Ca 2+和PKC依赖性PMN 对细胞外刺激的反应 在这篇文章中详细介绍了... al将在体外测试这一假设，使用PMNs和HL-60细胞刺激， 与fMLP，C5 a和LTB 4进行了标记，以检查多胺在 三个层次的行动： 第一章 化学引诱剂诱导的Ca 2+动员动力学的调节 是的。 这些影响的机制将通过评估 多胺对磷脂酰肌醇代谢和细胞功能的影响 Ca 2+通道、质膜Ca 2 +-ATP酶和钙小体。（二） PKC转位、激活和磷酸化的调节 蛋白质底物第三章 对Ca ~（2+）和PKC依赖性细胞的调节 活动，包括超氧化物的产生，分泌，肌动蛋白 聚合，调节细胞内PH，以及表达 化学引诱物受体 对宿主防御调节的这一新方面的研究将提供一个新的视角。 更好地理解致病基因的复杂机制- 牙周病发病与进展 由于多胺水平是 增加从其他发炎组织渗出，这些研究是 与其他类型炎症性疾病中的宿主防御调节相关， 放松。

Neutrophils (PMNs) are an essential component of the host defense in periodontal disease and other bacterial infections. PMN function is modulated by ligand binding to surface receptors, an event which gener- ates phosphoinositide hydrolysis products and transient increases in cytosolic Ca2+. These intracellular signals cooperate with each other to mobilize protein kinase C (PKC) and initiate many essential PMN activi- ties. Recent evidence suggests that Ca2+ signalling is significantly altered by polyamines, which are prevalent in the gingival fluid of inflamed periodontal pockets. Based on this evidence, we hypothesize that gingival fluid polyamines can significantly prolong the duration of both receptor-operated Ca2+ mobilization and_Ca2+-dependent-PKC mobiliza- tion, and thereby modulate many important Ca2+- and PKC-dependent PMN responses to extracellular stimuli. The studies detailed in this propos- al will test this hypothesis in vitro, using PMNs and HL-60 cells stimu- lated with fMLP, C5a, and LTB4 to examine the effects of polyamines at three levels of action: 1) Modulation of the kinetics of chemoattractant-induced Ca2+ mobiliza- tion. The mechanism of these effects will be examined by assessing polyamine effects on phosphoinositide metabolism and on the functions of Ca2+ channels, plasma membrane Ca2+-ATPases, and calciosomes. 2) Modulation of PKC translocation, activation and phosphorylation of cell protein substrates. 3) Modulation of Ca2+ - and PKC-dependent cell activities, including superoxide production, secretion, actin polymerization, regulation of intracellular PH, and expression of chemoattractant receptors. Study of this novel aspect of host defense modulation will provide a better understanding of the complex mechanisms involved in the pathogene- sis and progression of periodontal disease. Since polyamine levels are increased in exudates from other inflamed tissues, these studies are relevant to host defense modulation in other types of inflammatory dis- ease.