Production of proinflammatory cytokines by phorbol myristate acetate-treated THP-1 cells and monocyte-derived macrophages after phagocytosis of apoptotic CTLL-2 cells.
Production of proinflammatory cytokines by phorbol myristate acetate-treated THP-1 cells and monocyte-derived macrophages after phagocytosis of apoptotic CTLL-2 cells.
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佛波醇肉豆蔻酸酯醋酸酯处理的 THP-1 细胞和单核细胞衍生的巨噬细胞在吞噬凋亡的 CTLL-2 细胞后产生促炎细胞因子。
DOI：
10.4049/jimmunol.161.11.6245
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发表时间：
1998
影响因子：
4.4
通讯作者：
Y. Kobayashi
中科院分区：
文献类型：
--
作者：
K. Kurosaka;N. Watanabe;Y. Kobayashi
因为一般认为凋亡与炎症无关，我们假设吞噬细胞与凋亡细胞的相互作用为炎症提供了阴性或无效信号。然而，我们最近发现，虽然凋亡细胞膜似乎是完整的，但这种相互作用导致促炎细胞因子的产生，而不是促炎细胞因子的产生。在这项研究中，我们详细研究了巨噬细胞的细胞凋亡，吞噬和细胞因子的产生的动力学之间的关系。在检查的时间点中，在不存在IL-2的情况下培养12小时后，鼠CTLL-2细胞在细胞大小和磷脂酰丝氨酸暴露方面变得凋亡，同时它们开始被PMA处理的THP-1细胞（人巨噬细胞）吞噬并导致促炎细胞因子产生。通过共聚焦激光显微镜也证实了巨噬细胞对凋亡细胞的吞噬作用。人巨噬细胞与鼠凋亡细胞的共培养导致在mRNA水平和蛋白水平上产生人促炎细胞因子，特别是IL-8。单核细胞源性巨噬细胞与凋亡细胞的共培养也导致IL-8蛋白的产生。磷酸化L-丝氨酸或RGDS（Arg-Gly-Asp-Ser）均能抑制吞噬作用和细胞因子的产生，而RGES（Arg-Gly-Glu-Ser）则不能。因此，促炎细胞因子的产生和凋亡CTLL-2细胞的吞噬作用似乎是密切相关的。
Because it is generally believed that apoptosis is not associated with inflammation, we hypothesized that the interaction of phagocytes with apoptotic cells provides a negative or null signal for inflammation. However, we recently found that the interaction led to the production of proinflammatory cytokines but not antiinflammatory cytokines, although the apoptotic cell membranes appeared to be intact. In this study, we examined in detail the relationship among the kinetics of apoptosis, phagocytosis and production of cytokines by macrophages. Among the time points examined, murine CTLL-2 cells became apoptotic in terms of cell size and exposure of phosphatidylserine after 12 h of culture in the absence of IL-2, and at the same time they began to be phagocytosed and lead to proinflammatory cytokine production by PMA-treated THP-1 cells (human macrophages). The phagocytosis of apoptotic cells by macrophages was also confirmed by confocal laser microscopy. The coculturing of human macrophages with murine apoptotic cells led to the production of human proinflammatory cytokines, notably IL-8, at both the mRNA level and the protein level. The coculturing of monocyte-derived macrophages with the apoptotic cells also led to the production of IL-8 protein. Both the phagocytosis and production of the cytokines were suppressed by either phospho-L-serine or RGDS (Arg-Gly-Asp-Ser), but not by RGES (Arg-Gly-Glu-Ser). Thus, the production of proinflammatory cytokines and phagocytosis of apoptotic CTLL-2 cells appear to be closely interrelated.
影响因子：
4.4
作者：
V. Fadok;J. Savill;C. Haslett;D. Bratton;D. Doherty;Priscilla A. Campbell;Peter M. Henson
通讯作者：
V. Fadok;J. Savill;C. Haslett;D. Bratton;D. Doherty;Priscilla A. Campbell;Peter M. Henson
影响因子：
20.1
作者：
BENNETT, MR;GIBSON, DF;TAIT, JF
通讯作者：
TAIT, JF