Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation.
Transmigrating neutrophils shape the mucosal microenvironment through localized oxygen depletion to influence resolution of inflammation.
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DOI：
10.1016/j.immuni.2013.11.020
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发表时间：
2014-01-16
期刊：
影响因子：
32.4
通讯作者：
Colgan SP
中科院分区：
文献类型：
--
作者：
Campbell EL;Bruyninckx WJ;Kelly CJ;Glover LE;McNamee EN;Bowers BE;Bayless AJ;Scully M;Saeedi BJ;Golden-Mason L;Ehrentraut SF;Curtis VF;Burgess A;Garvey JF;Sorensen A;Nemenoff R;Jedlicka P;Taylor CT;Kominsky DJ;Colgan SP
急性肠道炎症涉及中性粒细胞 (PMN) 的早期积累，随后消退或进展为慢性炎症。根据最近的证据，粘膜代谢影响疾病结果，我们假设迁移的 PMN 影响周围粘膜的转录谱。微阵列研究揭示了一组受中性粒细胞-上皮细胞串扰调节的缺氧反应基因。迁移的中性粒细胞迅速耗尽微环境中的氧气，足以稳定肠上皮细胞缺氧诱导因子（HIF）。利用急性结肠炎模型中的 HIF 报告小鼠，我们研究了 PMN 和呼吸爆发对体内“炎症性缺氧”的相对贡献。与对照组相比，缺乏呼吸爆发的 CGD 小鼠结肠炎加重，PMN 浸润加剧，炎症性缺氧减少。最后，HIF 在粘膜内的药理学稳定性可保护 CGD 小鼠免受严重结肠炎的影响。总之，浸润中性粒细胞的转录印记通过局部耗氧来调节宿主对炎症的反应，导致微环境缺氧和有效的炎症消退。
Acute intestinal inflammation involves early accumulation of neutrophils (PMN) followed by either resolution or progression to chronic inflammation. Based on recent evidence mucosal metabolism influences disease outcomes, we hypothesized that transmigrating PMN influence the transcriptional profile of the surrounding mucosa. Microarray studies revealed a cohort of hypoxia-responsive genes regulated by PMN-epithelial crosstalk. Transmigrating PMN rapidly depleted microenvironmental O2 sufficiently to stabilize intestinal epithelial cell hypoxia-inducible factor (HIF). Utilizing HIF reporter mice in an acute colitis model, we investigated the relative contribution of PMN and the respiratory burst to “inflammatory hypoxia” in vivo. CGD mice, lacking a respiratory burst, developed accentuated colitis compared to control, with exaggerated PMN infiltration and diminished inflammatory hypoxia. Finally, pharmacological HIF stabilization within the mucosa protected CGD mice from severe colitis. In conclusion, transcriptional imprinting by infiltrating neutrophils modulates the host response to inflammation, via localized O2 depletion, resulting in microenvironmental hypoxia and effective inflammatory resolution.
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影响因子：
29.4
作者：
Cummins, Eoin P.;Seeballuck, Fergal;Taylor, Cormac T.
通讯作者：
Taylor, Cormac T.
DOI：
10.1038/nrgastro.2010.39
发表时间：
2010-05
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Bobrie, Angelique;Krumeich, Sophie;Thery, Clotilde
通讯作者：
Thery, Clotilde
DOI：
10.1152/ajpgi.00228.2009
发表时间：
2010-07-01
影响因子：
4.5
作者：
Beck, P. L.;Ihara, E.;Xavier, R. J.
通讯作者：
Xavier, R. J.
影响因子：
12.6
作者：
Huang, Jeannie S.;Noack, Deborah;Bastian, John
通讯作者：
Bastian, John