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Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.

Arjomandi M, Frelinger J, Donde A, Wong H, Yellamilli A, Raymond W - PLoS ONE (2011)

Bottom Line: Furthermore, we examined the relationship between airway sOPN and cellular inflammation.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.

View Article: PubMed Central - PubMed

Affiliation: 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

ABSTRACT

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.

Methodology: 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.

Principal findings: 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.

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Related in: MedlinePlus

Densitometry of sOPN in BAL.Absolute optical density adjusted for protein content of polymeric, monomeric, and cleaved sOPN in BAL fluid of healthy and asthmatic subjects.
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pone-0025678-g004: Densitometry of sOPN in BAL.Absolute optical density adjusted for protein content of polymeric, monomeric, and cleaved sOPN in BAL fluid of healthy and asthmatic subjects.

Mentions: Relative densitometry showed that compared to healthy subjects, asthmatic subjects had a proportionately lower fraction of polymeric sOPN and a higher fraction of monomeric sOPN in BAL and sputum samples (Tables 1 and 2). In addition, asthmatic subjects had a higher fraction of the 17 kD cleaved sOPN seen in the sputum samples (Table 2). Similarly, in BAL samples, absolute densitometry adjusted for protein concentration also showed that the OD of polymeric sOPN was significantly higher and the OD of monomeric sOPN was significantly lower in healthy subjects compared to that of asthmatic subjects (Figure 4). In induced sputum, absolute densitometry adjusted for protein concentration showed a higher fraction of the 17 kD cleaved sOPN band in asthmatic subjects (0.2±0.2 versus 0.1±0.1 densitometry unit/mg protein in asthmatic versus healthy subjects, respectively, Mann-Whitney p = 0.036), but no statistically significant difference was detected in other bands.


Secreted osteopontin is highly polymerized in human airways and fragmented in asthmatic airway secretions.

Arjomandi M, Frelinger J, Donde A, Wong H, Yellamilli A, Raymond W - PLoS ONE (2011)

Densitometry of sOPN in BAL.Absolute optical density adjusted for protein content of polymeric, monomeric, and cleaved sOPN in BAL fluid of healthy and asthmatic subjects.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198733&req=5

pone-0025678-g004: Densitometry of sOPN in BAL.Absolute optical density adjusted for protein content of polymeric, monomeric, and cleaved sOPN in BAL fluid of healthy and asthmatic subjects.
Mentions: Relative densitometry showed that compared to healthy subjects, asthmatic subjects had a proportionately lower fraction of polymeric sOPN and a higher fraction of monomeric sOPN in BAL and sputum samples (Tables 1 and 2). In addition, asthmatic subjects had a higher fraction of the 17 kD cleaved sOPN seen in the sputum samples (Table 2). Similarly, in BAL samples, absolute densitometry adjusted for protein concentration also showed that the OD of polymeric sOPN was significantly higher and the OD of monomeric sOPN was significantly lower in healthy subjects compared to that of asthmatic subjects (Figure 4). In induced sputum, absolute densitometry adjusted for protein concentration showed a higher fraction of the 17 kD cleaved sOPN band in asthmatic subjects (0.2±0.2 versus 0.1±0.1 densitometry unit/mg protein in asthmatic versus healthy subjects, respectively, Mann-Whitney p = 0.036), but no statistically significant difference was detected in other bands.

Bottom Line: Furthermore, we examined the relationship between airway sOPN and cellular inflammation.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.

View Article: PubMed Central - PubMed

Affiliation: 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

ABSTRACT

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.

Methodology: 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.

Principal findings: 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.

Show MeSH
Related in: MedlinePlus