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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

Alveolar macrophages and sOPN.Correlation between alveolar macrophage concentration (log base 2) and polymeric sOPN optical density (log base 2) in BAL (R = 0.61; p = 0.0007).
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pone-0025678-g005: Alveolar macrophages and sOPN.Correlation between alveolar macrophage concentration (log base 2) and polymeric sOPN optical density (log base 2) in BAL (R = 0.61; p = 0.0007).

Mentions: The inflammatory cell counts in BAL samples of subjects are shown in Table S2. In linear regression models, BAL polymeric sOPN concentration (as measured by absolute optical density) showed a significant association with increased cellularity in BAL (correlation coefficient R = 0.66; p = 0.0002) and in particular with alveolar macrophage concentration in BAL (Figure 5) (correlation coefficient R = 0.61; p = 0.0007). These models suggest that for every doubling concentration of polymeric sOPN in BAL, the leukocyte count in BAL increased by a factor of 24.0% (95% CI: 12.0% to 37.3%), and alveolar macrophage count in BAL increased by a factor of 22.1% (95% CI: 9.7% to 35.9%). Inclusion of age, sex, BMI, or BAL total protein concentration did not significantly affect the model. There was no association between inflammatory cells and monomeric or cleaved sOPN in BAL samples. The concentration of sOPN in sputum measured by densitometry did not correlate with sputum cell count.


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)

Alveolar macrophages and sOPN.Correlation between alveolar macrophage concentration (log base 2) and polymeric sOPN optical density (log base 2) in BAL (R = 0.61; p = 0.0007).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0025678-g005: Alveolar macrophages and sOPN.Correlation between alveolar macrophage concentration (log base 2) and polymeric sOPN optical density (log base 2) in BAL (R = 0.61; p = 0.0007).
Mentions: The inflammatory cell counts in BAL samples of subjects are shown in Table S2. In linear regression models, BAL polymeric sOPN concentration (as measured by absolute optical density) showed a significant association with increased cellularity in BAL (correlation coefficient R = 0.66; p = 0.0002) and in particular with alveolar macrophage concentration in BAL (Figure 5) (correlation coefficient R = 0.61; p = 0.0007). These models suggest that for every doubling concentration of polymeric sOPN in BAL, the leukocyte count in BAL increased by a factor of 24.0% (95% CI: 12.0% to 37.3%), and alveolar macrophage count in BAL increased by a factor of 22.1% (95% CI: 9.7% to 35.9%). Inclusion of age, sex, BMI, or BAL total protein concentration did not significantly affect the model. There was no association between inflammatory cells and monomeric or cleaved sOPN in BAL samples. The concentration of sOPN in sputum measured by densitometry did not correlate with sputum cell count.

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