Sputum Leucine-Rich Alpha-2 Glycoprotein as a Marker of Airway Inflammation in Asthma

PLoS One. 2016 Sep 9;11(9):e0162672. doi: 10.1371/journal.pone.0162672. eCollection 2016.

Abstract

Background: Asthma is a chronic inflammatory disease of airways, but an ideal biomarker that accurately reflects ongoing airway inflammation has not yet been established. The aim of this study was to examine the potential of sputum leucine-rich alpha-2 glycoprotein (LRG) as a new biomarker for airway inflammation in asthma.

Methods: We obtained induced sputum samples from patients with asthma (N = 64) and healthy volunteers (N = 22) and measured LRG concentration by sandwich enzyme-linked immunosorbent assay (ELISA). Ovalbumin (OVA)-induced asthma model mice were used to investigate the mechanism of LRG production during airway inflammation. The LRG concentrations in the bronchoalveolar lavage fluid (BALF) obtained from mice were determined by ELISA and mouse lung sections were stained with anti-LRG antibody and periodic acid-Schiff (PAS) reagent.

Results: Sputum LRG concentrations were significantly higher in patients with asthma than in healthy volunteers (p = 0.00686). Consistent with patients' data, BALF LRG levels in asthma model mice were significantly higher than in control mice (p = 0.00013). Immunohistochemistry of lung sections from asthma model mice revealed that LRG was intensely expressed in a subpopulation of bronchial epithelial cells, which corresponded with PAS-positive mucus producing cells.

Conclusion: These findings suggest that sputum LRG is a promising biomarker of local inflammation in asthma.

MeSH terms

  • Animals
  • Asthma / blood
  • Asthma / complications*
  • Asthma / metabolism*
  • Asthma / pathology
  • Biomarkers / blood
  • Bronchi / pathology
  • Bronchoalveolar Lavage Fluid
  • Cell Count
  • Disease Models, Animal
  • Epithelial Cells / metabolism
  • Female
  • Glycoproteins / blood
  • Glycoproteins / metabolism*
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Pneumonia / blood
  • Pneumonia / complications*
  • Pneumonia / metabolism*
  • Pneumonia / pathology
  • Sputum / metabolism*
  • Up-Regulation

Substances

  • Biomarkers
  • Glycoproteins
  • LRG1 protein, human

Grants and funding

This study was partly supported by the Grant-in-Aid for Scientific Research (C) (22591101) from the Japanese Ministry of Education, Culture, Sports, Science and Technology, the Grant-in-Aid for Scientist from the Ministry of Health, Labour and Welfare of Japan (H24-bio-ippan-002) and the Practical Research Project for Rare/Intractable Diseases from Japan Agency for Medical Research and Development (15ek0109045h0002).