Osteopontin is involved in migration of eosinophils in asthma.
BACKGROUND
Osteopontin (OPN) is an extracellular matrix protein with a wide range of functions, and is involved in various inflammatory diseases. However, the role of OPN in eosinophilic airway inflammation is unclear.


OBJECTIVE
To elucidate the role of OPN in eosinophilic airway inflammation.


METHODS
OPN protein levels in induced sputum from asthmatic patients and healthy controls were measured. Eosinophil migration assays were performed in the presence or absence of OPN, a blocking antibody (Ab) recognizing its integrin-binding domain (2K1) and an anti-integrin alpha 4 Ab (P1H4). In the mouse asthma model, the levels of eosinophilia were examined in bronchoalveolar lavage fluids (BALFs) from ovalbumin (OVA)-sensitized and -challenged mice with or without administration of an Ab (M5) corresponding to human 2K1.


RESULTS
Levels of OPN in induced sputum were significantly higher in asthmatic patients when compared with healthy controls. In addition, levels of OPN were correlated with the percentage of sputum eosinophils. OPN induced significant migration of human eosinophils and this effect was inhibited by 2K1 and P1H4. M5 significantly attenuated OVA-induced eosinophilia in BALFs.


CONCLUSIONS
These results indicate that OPN plays a role in the migration of eosinophils into the airways and may be involved in the pathogenesis of asthma.
Takahashi
A
A
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Hokkaido, Japan.
Kurokawa
M
M
Konno
S
S
Ito
K
K
Kon
S
S
Ashino
S
S
Nishimura
T
T
Uede
T
T
Hizawa
N
N
Huang
S-K
SK
Nishimura
M
M
D000328:Adult; D000368:Aged; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology / Q000601:surgery; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D053495:Osteopontin / Q000276:immunology*
D000906:Antibodies; D016207:Cytokines; D053495:Osteopontin