The nicotinic receptor Alpha7 impacts the mouse lung response to LPS through multiple mechanisms.
The nicotinic receptor Alpha7 impacts the mouse lung response to LPS through multiple mechanisms.
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DOI：
10.1371/journal.pone.0121128
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Gahring LC
中科院分区：
文献类型：
--
作者：
Enioutina EY;Myers EJ;Tvrdik P;Hoidal JR;Rogers SW;Gahring LC
烟碱乙酰胆碱受体α 7（α7）由全身的神经元和非神经元细胞表达。我们研究了鼻内（i.n.）脂多糖（LPS）受α7调节。这是在小鼠中使用同源重组在α7受体中引入点突变，用丙氨酸（α 7 E260 A）取代谷氨酸残基260，丙氨酸（α 7 E260 A）排列孔，这与控制该受体的异常钙离子电导有关。α 7 E260 A小鼠在i.n. LPS给药。这与α 7敲除（α 7 KO）不同，在α 7 KO中，i.n. LPS明显受损。虽然造血细胞被募集到α 7 E260 A小鼠的血流中，但它们不能有效地募集到肺的肺泡和肺泡腔中。骨髓重建实验表明，α 7 E260 A小鼠的CD 45+和CD 45-细胞的反应性均受损。在α 7 E260 A小鼠中，包括TNFα、IL-1α、Ccl 2和Cxcl 10在内的几种促炎细胞因子和趋化因子RNA的表达降低。然而，α 7 E260 A小鼠中CD 45-肺间质细胞的IL-13表达显著增加。我们的研究结果支持以下结论：α7功能多效性通过影响反映肺单个细胞组成的各种机制来调节组织对炎症损伤的反应。
The nicotinic acetylcholine receptor alpha7 (α7) is expressed by neuronal and non-neuronal cells throughout the body. We examined the mechanisms of the lung inflammatory response to intranasal (i.n.) lipopolysaccharide (LPS) regulated by α7. This was done in mice using homologous recombination to introduce a point mutation in the α7 receptor that replaces the glutamate residue 260 that lines the pore with alanine (α7E260A), which has been implicated in controlling the exceptional calcium ion conductance of this receptor. The α7E260A mice exhibit normal inflammatory cell recruitment to the blood in response to i.n. LPS administration. This differs from the α7knock-out (α7KO) in which upstream signaling to initiate the recruitment to the blood following i.n. LPS is significantly impaired. While hematopoietic cells are recruited to the bloodstream in the α7E260A mouse, they fail to be recruited efficiently into both the interstitium and alveolar spaces of the lung. Bone marrow reconstitution experiments demonstrate that the responsiveness of both CD45+ and CD45- cells of the α7E260A mouse are impaired. The expression of several pro-inflammatory cytokine and chemokine RNAs including TNFα, IL-1α, Ccl2 and Cxcl10 are decreased in the α7E260A mouse. However, there is a substantial increase in IL-13 expression by CD45- lung interstitial cells in the α7E260A mouse. Our results support the conclusion that α7 functional pleiotropy contributes to modulating the tissue response to an inflammatory insult through impacting upon a variety of mechanisms reflecting the individual cell composition of the lung.
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影响因子：
5.8
作者：
Papke RL
通讯作者：
Papke RL
DOI：
10.1152/ajplung.00031.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
Kasahara, Kazuki;Matsumura, Yoko;Kita, Eiji
通讯作者：
Kita, Eiji
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
33.6
作者：
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通讯作者：
Rogers SW
影响因子：
16.2
作者：
Corringer, PJ;Bertrand, S;Bertrand, D
通讯作者：
Bertrand, D