Chu H W, Kraft M, Krause J E, Rex M D, Martin R J
Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2000 Oct;106(4):713-22. doi: 10.1067/mai.2000.109829.
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.
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.
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.
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 FEV(1) 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).
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.
有研究表明神经机制在慢性哮喘的发病机制中起作用。P物质等神经肽的表达可能受包括支原体属在内的感染性病原体调节。与P物质不同，P物质受体神经激肽1在哮喘气道中的蛋白水平尚未得到研究。
本研究评估正常对照受试者和哮喘受试者支气管活检标本中P物质和神经激肽1的蛋白表达及黏液含量。同时对活检标本和支气管肺泡灌洗标本进行肺炎支原体检测。
收集10名正常对照受试者和18名哮喘受试者的活检标本，这些哮喘受试者在接受为期6周的大环内酯类抗生素（n = 11）或安慰剂（n = 7）治疗前后，对标本进行P物质、神经激肽1和黏液染色。通过聚合酶链反应评估肺炎支原体。
基线时，与正常对照受试者相比，哮喘受试者气道上皮中P物质和神经激肽1的表达及黏液含量增加。上皮黏液含量与上皮P物质表达相关（r(s)=0.45，P = 0.04），与预测的第1秒用力呼气容积百分比相关（r(s)= -0.51，P = 0.019）。抗生素治疗后，哮喘受试者上皮P物质和神经激肽1的表达均显著降低。18名哮喘受试者中有8名检测到肺炎支原体。与未感染肺炎支原体的哮喘受试者相比，感染肺炎支原体的哮喘受试者基线时上皮神经激肽1表达更高，抗生素治疗后显著降低（P = 0.02）。
我们的数据表明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此过程。抗生素干预可能部分通过下调神经源性过程对哮喘治疗有效。
