Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins
Sensitization of isolated rat vagal pulmonary sensory neurons by eosinophil-derived cationic proteins
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DOI：
10.1152/ajplung.00271.2007
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发表时间：
2008-03-01
影响因子：
4.9
通讯作者：
Lee, Lu-Yuan
中科院分区：
文献类型：
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作者：
Gu, Qihai;Wiggers, Michelle E.;Lee, Lu-Yuan
已有研究表明，吸入嗜酸性粒细胞衍生的阳离子蛋白可刺激麻醉大鼠的迷走神经C纤维，并显著增强其对肺充气的反应(Lee LY，Gu Q，Gleich GJ，J Appl Physiol 91：1318-1326,2001)。然而，这些影响是否源于这些蛋白质对感觉神经的直接作用尚不清楚。因此，本研究旨在确定这些蛋白对分离的大鼠迷走神经肺感觉神经元的影响。我们在穿孔全细胞膜片钳记录上的结果表明，嗜酸性粒细胞主要碱性蛋白(2µM，60 S)可显著增加辣椒素诱发的内向电流，这种作用在MBP后10min达到高峰，并持续60min，在电流钳模式下，MBP显著增加辣椒素和电刺激所诱发的动作电位数。MBP预处理不能显著改变这些感觉神经元的输入电阻。此外，当MBP的阳离子电荷被低分子肝素、聚L-谷氨酸或聚L-天冬氨酸等聚阴离子中和后，其致敏作用被完全消除。此外，其他嗜酸性粒细胞衍生蛋白(如嗜酸性粒细胞过氧化物酶)也产生类似的致敏作用。这些结果表明，阳离子蛋白对肺感觉神经元具有直接的、电荷依赖的和持久的敏化作用，这可能是在病理生理条件下与嗜酸性粒细胞的气道渗透相关的气道高反应性的原因。
It has been shown that airway exposure to eosinophil-derived cationic proteins stimulated vagal pulmonary C fibers and markedly potentiated their responses to lung inflation in anesthetized rats (Lee LY, Gu Q, Gleich GJ, J Appl Physiol 91: 1318-1326, 2001). However, whether the effects resulted from a direct action of these proteins on the sensory nerves was not known. The present study was therefore carried out to determine the effects of these proteins on isolated rat vagal pulmonary sensory neurons. Our results obtained from perforated whole cell patch-clamp recordings showed that pretreatment with eosinophil major basic protein (MBP; 2 mu M, 60 s) significantly increased the capsaicin-evoked inward current in these neurons; this effect peaked similar to 10 min after MBP and lasted for > 60 min; in current-clamp mode, MBP substantially increased the number of action potentials evoked by both capsaicin and electrical stimulation. Pretreatment with MBP did not significantly alter the input resistance of these sensory neurons. In addition, the sensitizing effect of MBP was completely abolished when its cationic charge was neutralized by mixing with a polyanion, such as low-molecular-weight heparin or poly-L-glutamic or poly-L-aspartic acid, before its delivery to the neurons. Moreover, a similar sensitizing effect was also generated by other eosinophil granule-derived proteins (e. g., eosinophil peroxidase). These results demonstrate a direct, charge-dependent, and long-lasting sensitizing effect of cationic proteins on pulmonary sensory neurons, which may contribute to the airway hyperresponsiveness associated with airway infiltration of eosinophils under pathophysiological conditions.