NLRP3 is essential for neutrophil polarization and chemotaxis in response to leukotriene B4 gradient

趋化性 炎症体 白三烯B4 细胞生物学 电池极性 先天免疫系统 方向性 炎症 运动性 活体显微镜检查 生物 细胞迁移 化学 免疫系统 免疫学 细胞 体内 生物化学 分子生物学 受体 生物技术
作者
Stijn Van Bruggen,P.A. Jarrot,Eline Thomas,Casey E. Sheehy,Camila M. Silva,Alan Y. Hsu,Pierre Cunin,Peter A. Nigrović,Edgar R. Gomes,Hongbo R. Luo,Clare M. Waterman,Denisa D. Wagner
出处
期刊:Proceedings of the National Academy of Sciences of the United States of America [Proceedings of the National Academy of Sciences]
卷期号:120 (35) 被引量:5
标识
DOI:10.1073/pnas.2303814120
摘要

Neutrophil recruitment to sites of infection and inflammation is an essential process in the early innate immune response. Upon activation, a subset of neutrophils rapidly assembles the multiprotein complex known as the NLRP3 inflammasome. The NLRP3 inflammasome forms at the microtubule organizing center, which promotes the formation of interleukin (IL)-1β and IL-18, essential cytokines in the immune response. We recently showed that mice deficient in NLRP3 (NLRP3 −/− ) have reduced neutrophil recruitment to the peritoneum in a model of thioglycolate-induced peritonitis. Here, we tested the hypothesis that this diminished recruitment could be, in part, the result of defects in neutrophil chemotaxis. We find that NLRP3 −/− neutrophils show loss of cell polarization, as well as reduced directionality and velocity of migration toward increasing concentrations of leukotriene B4 (LTB4) in a chemotaxis assay in vitro, which was confirmed through intravital microscopy of neutrophil migration toward a laser-induced burn injury of the liver. Furthermore, pharmacologically blocking NLRP3 inflammasome assembly with MCC950 in vitro reduced directionality but preserved nondirectional movement, indicating that inflammasome assembly is specifically required for polarization and directional chemotaxis, but not cell motility per se. In support of this, pharmacological breakdown of the microtubule cytoskeleton via nocodazole treatment induced cell polarization and restored nondirectional cell migration in NLRP3-deficient neutrophils in the LTB4 gradient. Therefore, NLRP3 inflammasome assembly is required for establishment of cell polarity to guide the directional chemotactic migration of neutrophils.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
玉米烤肠完成签到 ,获得积分10
2秒前
CipherSage应助小海采纳,获得10
3秒前
Chen_Liu应助mm采纳,获得10
7秒前
科研通AI2S应助mm采纳,获得10
7秒前
小青完成签到,获得积分10
9秒前
务实的语风完成签到,获得积分10
14秒前
14秒前
tuanheqi应助萧水白采纳,获得100
18秒前
21秒前
21秒前
爆米花应助高贵怀蕾采纳,获得10
21秒前
FashionBoy应助lerrygg采纳,获得20
23秒前
zzc完成签到 ,获得积分10
23秒前
汉堡包应助合适的灵枫采纳,获得10
24秒前
Z赵完成签到 ,获得积分10
27秒前
杭紫雪完成签到,获得积分10
29秒前
NexusExplorer应助天南采纳,获得30
30秒前
科研通AI2S应助super chan采纳,获得10
31秒前
33秒前
乐乐应助夜雨听笑采纳,获得10
33秒前
星辰大海应助Dazzein采纳,获得10
37秒前
37秒前
彭于晏应助沉默的含巧采纳,获得10
37秒前
凶狠的食铁兽完成签到,获得积分10
37秒前
37秒前
38秒前
41秒前
42秒前
44秒前
夜雨听笑发布了新的文献求助10
45秒前
Dazzein发布了新的文献求助10
46秒前
手机应助缥缈不惜采纳,获得10
46秒前
xiao牛完成签到,获得积分10
46秒前
48秒前
50秒前
53秒前
53秒前
zyzhnu完成签到,获得积分10
54秒前
烛夜黎发布了新的文献求助10
57秒前
58秒前
高分求助中
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger Heßler, Claudia, Rud 1000
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 1000
Natural History of Mantodea 螳螂的自然史 1000
A Photographic Guide to Mantis of China 常见螳螂野外识别手册 800
Autoregulatory progressive resistance exercise: linear versus a velocity-based flexible model 500
Spatial Political Economy: Uneven Development and the Production of Nature in Chile 400
Research on managing groups and teams 300
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3329457
求助须知:如何正确求助?哪些是违规求助? 2959146
关于积分的说明 8594359
捐赠科研通 2637590
什么是DOI,文献DOI怎么找? 1443651
科研通“疑难数据库(出版商)”最低求助积分说明 668775
邀请新用户注册赠送积分活动 656220