MONOCYTE SIGNALLING PATHWAYS IN APOPTOSIS AND ACTIVATION

在感染和炎症过程中，单核细胞从单核细胞中募集。 通过趋化因子循环到发炎组织，在那里它们被 多种炎症介质和基质成分。作为发起 药物被消除，炎症减弱，单核细胞不再是 这是必要的，必须从组织中去除以解决炎症。 在这个去除过程中的失败可能成为致病性的，并且许多慢性 炎性病症，包括类风湿性和实验诱导的 关节炎和破坏性牙周病与 炎症细胞的持续积累。因此了解 控制正常单核细胞缺失和潜能的机制 异常可能是调节策略发展的基础 慢性炎症病理学在这方面，细胞凋亡， 一种基本的机制，用于消除不需要的细胞， 活组织，可能在控制单核细胞聚集中发挥作用， 炎症性损伤在定义细胞内通路导致 单核细胞死亡，我们已经证明了至少两个离散的途径 调节涉及氧中间体（ROI）的单核细胞寿命， 蛋白激酶C（PKC）和Bc 1 -2。进一步解开这些二分法 单核细胞凋亡的途径不仅可以提供新的分子线索， 凋亡信号级联，但也确定了潜在的目标， 调节这个重要的炎症过程将这些研究扩展到 动物模型提供了令人兴奋的新数据， 细胞特异性和时间依赖性凋亡事件谱， 在细菌细胞壁诱导的关节炎的演变中起关键作用， 这与细胞凋亡途径失调的作用一致， 新的发病机制。

During infection and inflammation, monocytes are recruited from the circulation to inflamed tissues by chemokines where they are activated by multiple inflammatory mediators and matrix components. As the initiating agents are eliminated end inflammation wanes, the monocytes are no longer necessary and must be removed from the tissues to resolve inflammation. Failure in this removal process may become pathogenic, and many chronic inflammatory conditions, including rheumatoid and experimentally-induced arthritis and destructive periodontal disease are associated with the persistent accumulation of inflammatory cells. Therefore, understanding the mechanisms which control normal monocyte deletion and potential aberrancies may underlie the development of strategies for modulating chronic inflammatory pathology. In this regard, apoptosis which represents a fundamental mechanism for eliminating unwanted cells in the midst of living tissues, may play a role in controlling monocyte accumulation at an inflammatory lesion. In defining the intracellular pathways leading to monocyte death we have demonstrated at least two discrete pathways regulating monocyte life-span involving oxygen intermediates (ROI), protein kinase C (PKC), and Bc1-2. Further unraveling of these dichotomous routes of monocyte apoptosis may not only provide new molecular clues in the apoptotic signaling cascade, but also identify potential targets for regulating this crucial inflammatory process. Extending these studies to animal models has provided exciting new data which define an unique spectrum of cell specific and temporally dependent apoptotic events which are pivotal in the evolution of bacterial cell wall-induced arthritis, and which are consistent with a role for dysregulation of apoptotic pathways in emerging pathogenesis.