Neuropilin-2 regulates airway inflammatory responses to inhaled lipopolysaccharide
Neuropilin-2 regulates airway inflammatory responses to inhaled lipopolysaccharide
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DOI：
10.1152/ajplung.00067.2018
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发表时间：
2018-08-01
影响因子：
4.9
通讯作者：
Moran, Timothy P.
中科院分区：
文献类型：
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作者：
Immormino, Robert M.;Lauzier, David C.;Moran, Timothy P.
神经纤毛蛋白是一种多功能受体，在免疫调节中起重要作用。神经纤毛蛋白-2（NRP 2）在肺中表达，但它是否调节气道免疫反应尚不清楚。在这里，我们报告说，Nrp 2是弱表达的肺泡巨噬细胞（AM）在稳定状态下，但显着上调后，在体内脂多糖（LPS）吸入。用LPS离体处理人AM也增加NRP 2 mRNA表达和NRP 2蛋白的细胞表面展示。LPS诱导的Nrp 2在AM中的表达依赖于髓样分化初级反应88信号通路和转录因子NF-κ B。除了上调NRP 2在细胞膜上的展示外，吸入LPS还触发AM将可溶性NRP 2释放到气道中。最后，骨髓特异性消融NRP 2导致肺中趋化因子（C-C基序）配体2（Ccl 2）表达增加，并延长LPS吸入后气道中白细胞浸润。这些发现表明，AM的NRP 2表达调节LPS诱导的炎性细胞向气道的募集，并揭示了NRP 2在肺部先天免疫应答期间的新作用。
Neuropilins are multifunctional receptors that play important roles in immune regulation. Neuropilin-2 (NRP2) is expressed in the lungs, but whether it regulates airway immune responses is unknown. Here, we report that Nrp2 is weakly expressed by alveolar macrophages (AMs) in the steady state but is dramatically upregulated following in vivo lipopolysaccharide (LPS) inhalation. Ex vivo treatment of human AMs with LPS also increased NRP2 mRNA expression and cell-surface display of NRP2 protein. LPS-induced Nrp2 expression in AMs was dependent upon the myeloid differentiation primary response 88 signaling pathway and the transcription factor NF-kappa B. In addition to upregulating display of NRP2 on the cell membrane, inhaled LPS also triggered AMs to release soluble NRP2 into the airways. Finally, myeloid-specific ablation of NRP2 resulted in increased expression of the chemokine (C-C motif) ligand 2 (Ccl2) in the lungs and prolonged leukocyte infiltration in the airways following LPS inhalation. These findings suggest that NRP2 expression by AMs regulates LPS-induced inflammatory cell recruitment to the airways and reveal a novel role for NRP2 during innate immune responses in the lungs.