Substance P and its receptor neurokinin 1 expression in asthmatic airways

J Allergy Clin Immunol. 2000 Oct;106(4):713-22. doi: 10.1067/mai.2000.109829.

Abstract

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 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).

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Anti-Bacterial Agents / pharmacology
  • Asthma / etiology
  • Asthma / metabolism*
  • Biopsy
  • Bronchi / pathology
  • Epithelium / metabolism
  • Epithelium / microbiology
  • Female
  • Forced Expiratory Volume
  • Humans
  • Male
  • Mucus / chemistry
  • Mucus / microbiology
  • Mycoplasma pneumoniae / isolation & purification
  • Receptors, Neurokinin-1 / biosynthesis*
  • Substance P / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Receptors, Neurokinin-1
  • Substance P