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


CONCLUSIONS
These findings suggest that sputum LRG is a promising biomarker of local inflammation in asthma.
Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Hiromi
H
Honda
Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Minoru
M
Fujimoto
Department of Haematology and Respiratory Medicine, Kochi University, Nankoku-shi, Kochi, Japan.
Shintaro
S
Miyamoto
Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Minami-ku, Hiroshima, Japan.
Nobuhisa
N
Ishikawa
Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Satoshi
S
Serada
Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima, Japan.
Noboru
N
Hattori
Department of Animal Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, Japan.
Shintaro
S
Nomura
Department of Molecular and Internal Medicine, Graduate School of Biomedical Science, Hiroshima University, Minami-ku, Hiroshima, Japan.
Nobuoki
N
Kohno
Department of Haematology and Respiratory Medicine, Kochi University, Nankoku-shi, Kochi, Japan.
Akihito
A
Yokoyama
Division of Translational Research, Integrated Center for Advanced Medical Technologies (ICAM-Tech), Kochi Medical School, Kochi University, Nankoku-shi, Kochi, Japan.|Laboratory of Immune Signal, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Osaka, Japan.
Tetsuji
T
Naka
D000818:Animals; D001249:Asthma / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001980:Bronchi / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011014:Pneumonia / Q000097:blood / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D013183:Sputum / Q000378:metabolism*; D015854:Up-Regulation
D015415:Biomarkers; D006023:Glycoproteins; C015246:LRG1 protein, human