Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.
BACKGROUND
Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma.


METHODS
To determine whether secreted OPN (sOPN) is polymerized in human airways and whether it is qualitatively different in asthma, we used immunoblotting to examine sOPN in bronchoalveolar lavage (BAL) fluid samples from 12 healthy and 21 asthmatic subjects (and in sputum samples from 27 healthy and 21 asthmatic subjects). All asthmatic subjects had mild to moderate asthma and abstained from corticosteroids during the study. Furthermore, we examined the relationship between airway sOPN and cellular inflammation.


RESULTS
We found that sOPN in BAL fluid and sputum exists in polymeric, monomeric, and cleaved forms, with most of it in polymeric form. Compared to healthy subjects, asthmatic subjects had proportionately less polymeric sOPN and more monomeric and cleaved sOPN. Polymeric sOPN in BAL fluid was associated with increased alveolar macrophage counts in airways in all subjects.


CONCLUSIONS
These results suggest that sOPN in human airways (1) undergoes extensive post-translational modification by polymerization and proteolytic fragmentation, (2) is more fragmented and less polymerized in subjects with mild to moderate asthma, and (3) may contribute to recruitment or survival of alveolar macrophages.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America. mehrdad.arjomandi@ucsf.edu
Mehrdad
M
Arjomandi
Jessica
J
Frelinger
Aneesh
A
Donde
Hofer
H
Wong
Amritha
A
Yellamilli
Wilfred
W
Raymond
D000328:Adult; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D053495:Osteopontin / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D053495:Osteopontin