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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2
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Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2

机译：高度纯化的脂磷壁酸通过CD14和TLR2激活嗜中性粒细胞并延迟其自发凋亡

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Lipoteichoic acid (LTA) is a major component of the cell membrane of gram-positive bacteria. Although LTA has become increasingly recognized as an immunomodulator, its effect on polymorphonuclear neutrophil granulocytes (PMN) is still not clear. The interaction between LTA and PMN, however, is of particular importance, as PMN are the first leukocytes that migrate to the site of infection and encounter bacterial pathogens. In the present study, the interaction of highly purified human PMN with endotoxin-free LTA from Staphylococcus aureus was investigated. After exposure to LTA, neutrophil granulocytes acquired typical activated cell morphology. LTA had a marked activating effect on the functions of PMN as well. Shedding of CD62L, degranulation, and priming for formyl-Met-Leu-Phe-mediated oxidative burst were induced in PMN upon exposure to LTA. Moreover, LTA treatment induced the release of proinflammatory cytokines such as interleukin-8, tumor necrosis factor ?±, and granulocyte-colony stimulating factor by PMN. The effects of LTA on PMN were found to be associated with nuclear factor-?oB activation. Of particular interest was that LTA inhibited the spontaneous apoptosis and therefore, increased the lifespan of PMN. Experiments using blocking antibodies revealed that CD14 and Toll-like receptor 2 (TLR2) but not TLR4 play a major role in LTA-mediated effects on PMN. These data clearly show that LTA, a component of gram-positive bacteria, directly activates neutrophil granulocytes, the primary effector cells in the first line of defense against infectious challenge.
机译：脂磷壁酸（LTA）是革兰氏阳性细菌细胞膜的主要成分。尽管LTA已被越来越多地视为一种免疫调节剂，但其对多形核嗜中性粒细胞（PMN）的作用仍不清楚。然而，LTA和PMN之间的相互作用尤为重要，因为PMN是最早迁移到感染部位并遇到细菌病原体的白细胞。在本研究中，研究了高纯度人PMN与金黄色葡萄球菌的无内毒素LTA的相互作用。暴露于LTA后，中性粒细胞粒细胞获得了典型的活化细胞形态。 LTA对PMN的功能也有明显的激活作用。暴露于LTA的PMN诱导了CD62L的脱落，脱颗粒和甲酰-Met-Leu-Phe介导的氧化爆发的引发。此外，LTA处理诱导了PMN释放促炎细胞因子，例如白介素8，肿瘤坏死因子α±和粒细胞集落刺激因子。发现LTA对PMN的作用与核因子-αoB激活有关。特别令人感兴趣的是LTA抑制了自发凋亡，因此增加了PMN的寿命。使用封闭抗体的实验表明，CD14和Toll样受体2（TLR2）而非TLR4在LTA介导的PMN效应中起主要作用。这些数据清楚地表明，LTA是革兰氏阳性细菌的组成部分，可以直接激活嗜中性粒细胞，这是抵抗传染性攻击的第一道防线。

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