Substance P and its receptor neurokinin 1 expression in asthmatic airways
Substance P and its receptor neurokinin 1 expression in asthmatic airways
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DOI：
10.1067/mai.2000.109829
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发表时间：
2000-10-01
影响因子：
14.2
通讯作者：
Martin, RJ
中科院分区：
文献类型：
--
作者：
Chu, HW;Kraft, M;Martin, RJ
研究背景：慢性哮喘的发病机制可能与神经机制有关，P物质等神经肽的表达可能受支原体等感染性病原体的调控。与P物质相反，P物质受体神经激肽1尚未在哮喘气道的蛋白质水平上进行检测。目的：研究正常对照和哮喘患者支气管活检标本中P物质和神经激肽1蛋白的表达及黏液含量。方法：在大环内酯类抗生素（n = 11）或安慰剂（n = 7）治疗6周前后，分别采集10例正常对照和18例哮喘患者的活检标本，进行P物质、神经激肽1和粘液染色。结果：在基线时，与正常对照组相比，哮喘组气道上皮P物质和神经激肽1的表达增加，粘液含量增加。上皮黏液含量与上皮物质P表达相关（r(s) = 0.45, P = 0.04），预测fev1% （r(s) = -0.51, P = 0.019）。抗生素治疗后，哮喘患者上皮物质P和神经激肽1的表达均显著降低。18例哮喘患者中有8例检出肺炎支原体，合并肺炎支原体的哮喘患者与未合并肺炎支原体的哮喘患者相比，上皮神经激肽1的基线表达较高，经抗生素治疗后显著降低（P = 0.02）。结论：我们的数据提示哮喘气道上皮可能存在神经机制异常，肺炎支原体可能参与了这一过程。抗生素干预可能是有效的治疗哮喘部分通过下调神经源性过程。
Background: Neural mechanisms have been suggested to contribute to the pathogenesis of chronic asthma, The expression of neuropeptides such as substance P may be regulated by infectious pathogens, including Mycoplasma species. In contrast to substance P, the substance P receptor neurokinin 1 has not been examined at the protein level in asthmatic airways.Objective: This study evaluated substance P and neurokinin 1 protein expression and mucus content in endobronchial biopsy specimens from normal control subjects and asthmatic subjects. Detection of Mycoplasma pneumoniae was performed in both biopsy and bronchoalveolar lavage specimens,Methods: Biopsy specimens were collected from 10 normal control subjects and 18 asthmatic subjects before and after a 6-week treatment with a macrolide antibiotic (n = 11) or placebo (n = 7) and were stained for substance P, neurokinin 1, and mucus. M pneumoniae was evaluated by PCR,Results: At baseline, compared with normal control subjects, asthmatic subjects demonstrated increased expression of substance P and neurokinin 1 and mucus content in the airway epithelium. Epithelial mucus content correlated with epithelial substance P expression (r(s) = 0.45, P =.04) and FEV1 percent predicted (r(s) = -0.51, P = .019). After antibiotic treatment, both epithelial substance P and neurokinin 1 expression were significantly reduced in asthmatic subjects. M pneumoniae was found in 8 of 18 asthmatic subjects, Asthmatic subjects with M pneumoniae, compared with those without M pneumoniae, showed higher baseline epithelial neurokinin 1 expression, which was significantly reduced after antibiotic treatment (P = .02).Conclusion: Our data suggest that abnormalities in neural mechanisms may exist in the epithelium of asthmatic airways, and M pneumoniae is possibly involved in this process. Antibiotic intervention may be effective in the treatment of asthma partly through the downregulation of the neurogenic process.