Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages.
Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages.
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DOI：
10.1038/cddis.2011.13
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发表时间：
2011-03-17
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
嗜中性粒细胞的肺部蓄积是活跃吸烟者的典型特征，他们也易患多种炎症性和感染性肺部疾病。我们发现，人类中性粒细胞暴露于香烟烟雾提取物（CSE）导致非典型细胞死亡的细胞凋亡，自噬和坏死的共享功能。焦油样物质在自噬体中的积累也很明显。在检测确定的细胞死亡标志物之前，CSE处理的嗜中性粒细胞被单核细胞衍生的巨噬细胞有效识别和非吞噬性吞噬。阻断LOX-1和清道夫受体A，但不阻断MARCO或CD 36，以及与oxLDL预孵育，抑制吞噬作用，表明oxLDL样结构是主要的吞噬信号。特定的脂质（β-胡萝卜素和槲皮素），但不是水，抗氧化剂增加CSE的促吞噬作用。与非炎性吞噬作用相反，通过乳铁蛋白释放监测的次级颗粒的脱粒在CSE暴露时是明显的，这可能促进肺部炎症和组织降解。此外，暴露于CSE的中性粒细胞摄取呼吸道病原体金黄色葡萄球菌的能力受损，这可能导致吸烟者肺部的细菌持续存在，并可能促进中性粒细胞的进一步肺部募集。这些数据提供了对吸烟者肺中缺乏凋亡中性粒细胞群体积累及其对降解性肺部疾病和细菌感染的易感性增加的机制性见解。
Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections.
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影响因子：
3.9
作者：
Hwang, Jae-woong;Chung, Sangwoon;Sundar, Isaac K.;Yao, Hongwei;Arunachalam, Gnanapragasam;McBurney, Michael W.;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
5.5
作者：
Langereis, Jeroen D.;Raaijmakers, Hanneke A. J. A.;Koenderman, Leo
通讯作者：
Koenderman, Leo
DOI：
10.1016/0006-291x(73)90673-6
发表时间：
1973-01-01
影响因子：
3.1
作者：
BIETH, J;WERMUTH, CG
通讯作者：
WERMUTH, CG
影响因子：
24.3
作者：
Pletz, MWR;Ioanas, M;Lode, H
通讯作者：
Lode, H
影响因子：
10
作者：
O'Donnell, RA;Peebles, C;Djukanovic, R
通讯作者：
Djukanovic, R