Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.
Bone marrow transplantation reveals an essential synergy between neuronal and hemopoietic cell neurokinin production in pulmonary inflammation.
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骨髓移植揭示了肺部炎症中神经元和造血细胞神经激肽产生之间的重要协同作用。
DOI：
10.1172/jci17458
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Fontan,JJulioPerez
中科院分区：
文献类型：
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作者：
Chavolla-Calderon,Mara;Bayer,MegganK;Fontan,JJulioPerez
神经源性炎症被认为起源于有害刺激后无髓鞘神经纤维（C纤维）中P物质和前速激肽A（PPT-A）基因编码的其他神经激肽的逆行释放。与这一概念相一致，我们在这里表明，选择性感觉纤维去神经与辣椒素和有针对性的删除PPT-A基因保护小鼠肺免疫复合物介导的和拉伸介导的损伤。用WT骨髓重建PPT-A基因缺失的小鼠并没有消除这种保护作用，证明了感觉神经元在肺部炎症中PPT-A基因表达的关键作用。令人惊讶的是，用PPT-A基因缺陷的骨髓重建WT小鼠也赋予了对肺损伤的保护，揭示了PPT-A基因在造血细胞中的表达在组织损伤中具有先前未预料到的重要作用。两者合计，这些研究结果表明辣椒素敏感的感觉纤维和造血细胞之间的神经激肽介导的炎症的关键协同作用，并表明这种协同作用可能是一个刻板的机制，在呼吸道损伤的反应的基础。
Neurogenic inflammation is believed to originate with the antidromic release of substance P, and of other neurokinins encoded by the preprotachykinin A (PPT-A) gene, from unmyelinated nerve fibers (C-fibers) following noxious stimuli. Consistent with this concept, we show here that selective sensory-fiber denervation with capsaicin and targeted deletion of the PPT-A gene protect murine lungs against both immune complex–mediated and stretch-mediated injuries. Reconstitution of PPT-A gene–deleted mice with WT bone marrow does not abrogate this protection, demonstrating a critical role for PPT-A gene expression by sensory neurons in pulmonary inflammation. Surprisingly, reconstitution of WT mice with PPT-A gene–deficient bone marrow also confers protection against pulmonary injury, revealing that PPT-A gene expression in hemopoietic cells has a previously unanticipated essential role in tissue injury. Taken together, these findings demonstrate a critical synergy between capsaicin-sensitive sensory fibers and hemopoietic cells in neurokinin-mediated inflammation and suggest that such synergy may be the basis for a stereotypical mechanism of response to injury in the respiratory tract.