LPS-MONOCYTE INTERACTIONS IN PERIODONTAL DISEASE

人单核吞噬细胞（HMP）可以在升高的数量中鉴定， 牙周病组织，并可以刺激释放 生理上显著量的花生四烯酸（AA）代谢物 包括前列腺素E2（PGE 2）和血栓素B2（TSB 2）。 PGE 2具有 特别是与牙周病的关系，因为它的能力， 刺激骨吸收和调节免疫功能。 细菌 内毒素是一种复杂的脂多糖（LPS），参与了 牙周病的发病机制，是一个强大的刺激AA HMP的代谢产物释放。 然而，LPS的机制 HMP中AA代谢的调节几乎还未被探索。 的目标 该建议详细研究了AA代谢物释放的LPS调节 HMP的。 本提案中要解决的具体问题包括：1）LPS 在不存在C3 b的情况下刺激AA代谢物从HMP释放 刺激作用，2）PGE 2的明显细胞区室化 以及LPS刺激后HMP产生和释放TXB 2， 以及3）HMP是否具有显著量的醚酰基和烷基酰基 磷脂和LPS是否选择性地调节AA从这些释放 脂质。 初始实验将表征时间和剂量依赖性 用几种LPS刺激后HMP的代谢物释放 包括LPS的生物活性脂质A部分的制剂。 AA 代谢物释放将通过RIA以及通过产生 用3 H-AA和/或14 C-AA预标记HMP后标记的代谢物。 此外，HMP磷脂含量将被广泛表征 特别强调醚酰基和烷基酰基磷脂含量。 然后将标记代谢物出现的时间过程关联起来 磷脂标记的改变。 这些研究将提供 对LPS和HMP之间的生物相互作用的进一步了解， 将为单核细胞/巨噬细胞在 慢性炎症性疾病过程，包括牙周病。

Human mononuclear phagocytes (HMP) can be identified in elevated numbers in periodontally diseased tissues and can be stimulated to release physiologically significant amounts of arachidonic acid (AA) metabolites including prostaglandin E2 (PGE2) and thromboxane B2 (TSB2). PGE2 has particular relevance to periodontal disease due to its capacity to stimulate bone resorption and regulate immune function. Bacterial endotoxin, a complex lipopolysaccharide (LPS) implicated in the pathogenisis of periodontal disease, is a potent stimulator of AA metabolite release from HMP. However, the mechanisms by which LPS regulates AA metabolism in HMP remains virtually unexplored. The goal of this proposal is examine in detail LPS regulation of AA metabolite release from HMP. Specific points to be addressed in this proposal include 1) LPS stimulation of AA metabolite release from HMP in the absence of C3b stimulatory effects, 2) the apparent cellular compartmentalization of PGE2 and TXB2 production and release from HMP following stimulation with LPS, and 3) whether HMP possess significant amounts of ether-acyl and alkyl-acyl phospholipids and whether LPS selectively regulates AA release from these lipids. Initial experiments will characterize time and dose dependent metabolite release from HMP following stimulation with several LPS preparations including the biologically active lipid A moiety of LPS. AA metabolite release will be monitored by RIA as well as by the production of labelled metabolites following HMP prelabelling with 3H-AA and/or 14C-AA. In addition, HMP phospholipid content will be extensively characterized with specific emphasis on ether-acyl and alkyl-acyl phospholipid content. The time course of labelled metabolite appearance will then be correlated with alterations in phospholipid labelling. These studies will provide additional insight into the biological interaction between LPS and HMP and will provide additional support for the role of the monocyte/macrophage in chronic inflammatory disease processes including periodontal disease.