Neutrophils counteract autophagy-mediated anti-inflammatory mechanisms in alveolar macrophage: role in posthemorrhagic shock acute lung inflammation.
Neutrophils counteract autophagy-mediated anti-inflammatory mechanisms in alveolar macrophage: role in posthemorrhagic shock acute lung inflammation.
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中性粒细胞抵消肺泡巨噬细胞中自噬介导的抗炎机制：在失血后休克急性肺部炎症中的作用
DOI：
10.4049/jimmunol.1400899
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Wen Z;Fan L;Li Y;Zou Z;Scott MJ;Xiao G;Li S;Billiar TR;Wilson MA;Shi X;Fan J
急性肺损伤（ALI）是大手术和创伤引起的失血性休克（HS）后多器官功能障碍综合征的主要组成部分。 HS 患者对 ALI 发展的易感性增加表明尚未完全阐明增强肺部促炎反应和/或抑制抗炎反应的机制。肺泡巨噬细胞 (AMφ) 是 HS 后 ALI 发病机制的核心。我们之前报道过 HS 激活的多形核中性粒细胞 (PMN) 与巨噬细胞相互作用，影响炎症进展。在这项研究中，我们探索了 PMN 调节 AMφ 抗炎机制（涉及自噬）的新功能。使用HS/复苏的小鼠“两次打击”模型，然后气管内注射胞壁酰二肽，我们证明HS启动高迁移率族盒1/TLR4信号传导，上调AMφ中的NOD2表达，并使它们对随后的NOD2配体胞壁酰二肽敏感，从而增强肺部炎症。此外，上调的 NOD2 信号传导会诱导 AMφ 中的自噬，从而通过 NOD2-RIP2 信号传导和炎症小体激活的反馈抑制来负向调节肺部炎症。重要的是，我们进一步证明，在肺泡中迁移的 HS 激活的 PMN 可能通过 NAD(P)H 氧化酶介导的信号传导来增强 I-κB 激酶 γ 磷酸化、NF-κB 激活和核苷酸结合寡聚化结构域蛋白 3 炎症小体激活，从而抵消 AMφ 中自噬的抗炎作用，从而增强 HS 后肺部炎症。这些发现探索了 ALI 机制中先前未发现的复杂性，其中涉及细胞间相互作用和受体串扰。
Acute lung injury (ALI) is a major component of multiple organ dysfunction syndrome after hemorrhagic shock (HS) resulting from major surgery and trauma. The increased susceptibility in HS patients to the development of ALI suggests not yet fully elucidated mechanisms that enhance proinflammatory responses and/or suppress anti-inflammatory responses in the lung. Alveolar macrophages (AMϕ) are at the center of the pathogenesis of ALI after HS. We have previously reported that HS-activated polymorphonuclear neutrophils (PMNs) interact with macrophages to influence inflammation progress. In this study, we explore a novel function of PMNs regulating AMϕ anti-inflammatory mechanisms involving autophagy. Using a mouse “two-hit” model of HS/resuscitation followed by intratracheal injection of muramyl dipeptide, we demonstrate that HS initiates high mobility group box 1/TLR4 signaling, which upregulates NOD2 expression in AMϕ and sensitizes them to subsequent NOD2 ligand muramyl dipeptide to augment lung inflammation. In addition, upregulated NOD2 signaling induces autophagy in AMϕ, which negatively regulates lung inflammation through feedback suppression of NOD2-RIP2 signaling and inflammasome activation. Importantly, we further demonstrate that HS-activated PMNs that migrate in alveoli counteract the anti-inflammatory effect of autophagy in AMϕ, possibly through NAD(P)H oxidase–mediated signaling to enhance I-κB kinase γ phosphorylation, NF-κB activation, and nucleotide-binding oligomerization domain protein 3 inflammasome activation, and therefore augment post-HS lung inflammation. These findings explore a previously unidentified complexity in the mechanisms of ALI, which involves cell–cell interaction and receptor cross talk.
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影响因子：
4.8
作者：
Bertin, J;Nir, WJ;DiStefano, PS
通讯作者：
DiStefano, PS
影响因子：
6
作者：
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DOI：
10.1152/ajplung.00359.2004
发表时间：
2005-05-01
影响因子：
4.9
作者：
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影响因子：
4.4
作者：
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作者：
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