PERIODONTAL SHORT CHAIN FATTY ACIDS TOXIC TO PMNS

多形核白细胞(PMN)是 蜂窝宿主防御系统。应对感染中性粒细胞 表现出细胞功能序列的增加，包括： 黏附、趋化、吞噬、脱颗粒，最终 细菌致死。这些响应中的前四个涉及细胞 能动性，因此依赖于持续、有序、长期 肌动蛋白细胞骨架的重组。积累数据 表明受体-配体的相互作用启动了这些细胞 回应。此外，以下非常早期的事件 受体-配体相互作用包括立即、快速、 肌动蛋白细胞骨架和细胞内的一过性改变 PH值。 在单独但相关的文献中，临床数据表明 被认为会导致牙周病的厌氧细菌 感染会释放短链脂肪酸。(SCFA)进入他们的 环境。这些单链脂肪酸已被证明能抑制中性粒细胞的运动 功能。 因此，我们有兴趣回答以下分子问题 问题： 1.单链脂肪酸是否会改变中性粒细胞肌动蛋白细胞骨架？ 2.单链脂肪酸是否会改变PMN的内部pH？和 3.单链脂肪酸是否会改变中性粒细胞趋化肽受体？ 如果拟议工作的结果表明，专题小组委员会 对PMN有有害影响，还有几个问题 将引起极大的临床兴趣：现场存在哪些单链脂肪酸 患有活动性牙周炎？SCFA对其他方面的影响是什么 牙周组织的细胞？最后，细菌细胞能否 哪些产品降低了超临界脂肪酸的产量？

Polymorphonuclear leukocytes (PMNs) are the infantry of the cellular host defense system. In response to infections PMNs exhibit an increase in a sequence of cell functions which include: adhesion, chemotaxis, phagocytosis, degranulation, and ultimately bacterial killing. The first four of these responses involve cell motility, and therefore depend on continued, orderly, long-term reorganizations of the actin cytoskeleton. Accumulating data indicate that receptor-ligand interactions initiate these cellular responses. Furthermore, the very early events following receptor-ligand interaction include an immediate, rapid, transient, alteration in the actin cytoskeleton and intracellular pH. In separate but related literature, clinical data indicate that anaerobic bacteria which are thought to cause periodonatal infections release short chain fatty acids. (SCFA) into their environment. These SCFA have been shown to inhibit PMN motile functions. We are therefore interested in answering the following molecular questions: 1. Do SCFAs alter the PMN actin cytoskeleton? 2. Do SCFAs alter the internal pH of the PMN? and 3. Do SCFAs alter PMN chemotactic peptide receptors? If the results of the proposed work indicate that the SCFAs do have a deleterious effect on PMNs, several additional questions will be of great clinical interest: What SCFAs are present in sites with active periodontitis? What is the effect of SCFA on other cells of the periodontium? and finally, Can bacterial cells be engineered which have reduced SCFA production?