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

细胞凋亡是指在胚胎发育和成体发育过程中将不需要的细胞从活体中清除的一种生理性细胞死亡过程。它还在调节慢性炎性病变中炎性细胞的存活方面发挥作用。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和作用。胸腺细胞的凋亡被发现至少受两个步骤的蛋白磷酸化调控：一个是触发细胞凋亡，另一个是参与细胞凋亡的进行。后一种蛋白的磷酸化发生在该过程的后期，似乎是由各种刺激诱导的细胞凋亡所共有的。蛋白酶体抑制剂可抑制多种刺激诱导的胸腺细胞凋亡，提示蛋白水解酶在胸腺细胞凋亡中起重要作用。放线菌酮可部分抑制地塞米松诱导的脾T细胞凋亡，但放线菌酮本身可抑制…更多地诱导细胞凋亡。因此，成熟T细胞存在两种凋亡机制，一种是蛋白质合成依赖性的，另一种是非依赖性的。脾T细胞对TPA或A23187具有抵抗力，可诱导胸腺细胞发生凋亡。然而，T细胞在IL-2存在下培养3天后对A23187相对敏感，这表明激活诱导的细胞死亡部分是由钙介导的信号诱导的。停用IL-2后，依赖IL-2的CTLL-2细胞发生凋亡，同时核蛋白酪氨酸磷酸化水平降低。IL-2的耗竭是激活诱导的细胞死亡的原因之一，参与了炎症的消退。胸腺细胞和T细胞凋亡的分子机制尚需进一步研究。当血清耗尽时，单核细胞和巨噬细胞系、U937和P388D1细胞发生凋亡。肿瘤坏死因子-α或P物质可抑制细胞凋亡，并伴有蛋白酪氨酸磷酸化的增加。这些结果表明，细胞因子或神经肽通过调节炎症细胞的生存来调节炎症反应。较少

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 IL-2-dependent CTLL-2 cells underwent apoptosis when IL-2 was withdrawn accompanying by decreased in protein tyrosine phosphorylation in nuclear protein.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