Apoptosis of macrophages and T cells in periodontal tissues : Its molecular mechanisms and biological roles

细胞凋亡是一种生理细胞死亡过程，在胚胎发生和成体发育过程中从生物体中清除不需要的细胞。它还在慢性炎性病变中调节炎症细胞的存活。本研究旨在阐明在牙周炎中起重要作用的单核细胞、巨噬细胞和T细胞凋亡的分子机制及其作用。胸腺细胞凋亡被发现受蛋白磷酸化至少两个步骤的调节；一个触发细胞凋亡，另一个参与细胞凋亡进程。后一种蛋白磷酸化发生在该过程的较晚阶段，似乎在各种刺激诱导的细胞凋亡中很常见。多种刺激诱导的胸腺细胞凋亡可被蛋白酶体抑制剂所抑制，提示蛋白酶在细胞凋亡中起重要作用。环己亚胺能部分抑制地塞米松诱导的脾T细胞凋亡，但环己亚胺本身更能诱导细胞凋亡。因此，成熟T细胞的凋亡存在两种机制，蛋白质合成依赖性和非依赖性。脾T细胞对TPA和A23187均有耐药性，并能诱导胸腺细胞凋亡。然而，在IL-2存在下培养3天后，T细胞对A23187变得相对敏感，这表明激活诱导的细胞死亡在一定程度上是由钙介导的信号传导诱导的。IL-2停用后，核蛋白酪氨酸磷酸化水平降低，导致依赖IL-2的CTLL-2细胞发生凋亡。IL-2的消耗是激活诱导的细胞死亡的一个原因，它参与了炎症的解决。胸腺细胞和T细胞凋亡的分子机制有待进一步研究。单核细胞和巨噬细胞、U937和P388D1细胞在血清缺失时发生凋亡。细胞凋亡被tnf - α或P物质抑制，同时酪氨酸蛋白磷酸化增加。结果表明，细胞因子或神经肽通过调节炎症细胞的存活来调节炎症反应。少

Apoptosis is a physiological cell death process of eliminating unwanted cells from living organisms during embryogenic and adult development. It also function in regulation of survival of inflammatory cells in chronic inflammatory lesions. The aims of the present study are to elucidate the molecular mechanisms and roles of apoptosis of monocytes, macrophages and T cells which play important roles in periodontitis. Thymocyte apoptosis is found to be regulated by at least two steps of protein phosphorylation ; one is triggering apoptosis, another is involved in progressing apoptosis. The latter protein phosphorylation occurs at a later stage of the process and seems to be common to the apoptosis induced by various stimuli. Thymocyte apoptosis induced by various stimuli was inhibited by inhibitors of proteasome, suggesting an important role of proteases in apoptosis. Apoptosis induced by dexamethasone in spleen T cells was paritially inhibited by cycloheximide, though cycloheximide itself … More induced apoptosis. Thus, there exist two mechanisms of apoptosis in mature T cells, protein synthesis-dependent and-independent. Spleen T cells were resistant to TPA or A23187 which was able to induce apoptosis in thymocytes. However, T cells bacame relatively sensitive to A23187 after cultivation for 3 days in the presence of IL-2, suggesting that activation-induced cell death is induced in part by calcium-mediated signaling. IL-2-dependent CTLL-2 cells underwent apoptosis when IL-2 was withdrawn accompanying by decreased in protein tyrosine phosphorylation in nuclear protein. Depletion of IL-2 is a cause of activation-induced cell death which participates in resolution of inflammation. Further studies on the molecular mechanisms of apoptosis in thymocytes and T cells are required. Monocyte and macroophage cell lines, U937 and P388D1 cells underwent apoptosis when serum was depleted. The apoptosis was inhibited by TNF-alpha or substance P accompanying by increased protein tyrosine phosphorylation. The results suggest cytokines or neuropeptides modualate inflammatory responses through regulating survival of inflammatory cells. Less