Microbial antigen triggers rapid mobilization of TNF-α to the surface of mouse neutrophils transforming them into inducers of high-level dendritic cell TNF-α production
Microbial antigen triggers rapid mobilization of TNF-α to the surface of mouse neutrophils transforming them into inducers of high-level dendritic cell TNF-α production
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DOI：
10.4049/jimmunol.174.8.4845
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发表时间：
2005-04-15
影响因子：
4.4
通讯作者：
Denkers, EY
中科院分区：
文献类型：
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作者：
Bennouna, S;Denkers, EY
中性粒细胞在对许多微生物病原体的早期免疫中起关键作用，这可能部分是由于它们在感染期间释放免疫调节细胞因子和趋化因子的能力。在这里，我们通过流式细胞术分析表明，小鼠多形核白细胞（PMN）上调表面表达TNF-α在10分钟内的刺激与LPS，这是随后逐渐损失超过18小时的一段时间。表面TNF-α表达的早期增加与预先形成的TNF-α的细胞内池的损失相关。然而，延长与LPS的孵育导致TNF-α mRNA合成水平的增加和细胞内细胞因子的补充。在用LPS触发后，PMN获得诱导树突状细胞（DC）产生TNF-α和IL-12的能力。Transwell分析表明，LPS触发的中性粒细胞诱导的高水平DC TNF-α产生依赖于细胞间接触和中性粒细胞TNF-α，但中性粒细胞指令DC IL-12合成均不需要。这些数据表明，微生物Ag触发的小鼠PMN获得的能力，提供强有力的DC激活信号，通过阐述细胞因子和直接相互作用在细胞表面。
Neutrophils play a critical role in early immunity to many microbial pathogens, and this may in part be due to their ability to release immunoregulatory cytokines and chemokines during infection. Here, we demonstrate by flow cytometric analysis that mouse polymorphonuclear leukocytes (PMN) up-regulate surface expression of TNF-alpha within 10 min of stimulation with LPS, and that this is followed by gradual loss over a period of 18 h. Early increases in surface TNF-alpha expression correlated with loss of intracellular pools of preformed TNF-alpha. Nevertheless, extended incubation with LPS resulted in increased levels of TNF-alpha mRNA synthesis and replenishment of intracellular cytokine. After triggering with LPS, PMN acquired the ability to induce dendritic cell (DC) TNF-alpha and IL-12 production. Transwell assays demonstrated that high-level DC TNF-alpha production induced by LPS-triggered neutrophils was dependent upon cell-to-cell contact and neutrophil TNF-alpha, but neither was required for neutrophil instruction of DC IL-12 synthesis. The data suggest that microbial Ag-triggered mouse PMN acquire the capacity to deliver potent DC-activating signals through elaboration of cytokines and direct interactions at the cell surface.