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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

Secreted OPN in BAL and sputum.Relative optical density of polymeric, monomeric, and cleaved sOPN in BAL fluid and induced sputum of healthy and asthmatic subjects. White: polymeric sOPN (≥90 kD); light gray: monomeric sOPN (50–55 kD); dark gray: cleaved sOPN (25 kD); black: cleaved sOPN (17 kD).
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pone-0025678-g003: Secreted OPN in BAL and sputum.Relative optical density of polymeric, monomeric, and cleaved sOPN in BAL fluid and induced sputum of healthy and asthmatic subjects. White: polymeric sOPN (≥90 kD); light gray: monomeric sOPN (50–55 kD); dark gray: cleaved sOPN (25 kD); black: cleaved sOPN (17 kD).

Mentions: Relative densitometry of the individual BAL and sputum samples from each subject showed that the intensity of the polymeric sOPN bands was much higher relative to the intensity of the other forms of sOPN, suggesting that most of sOPN in BAL and sputum is in polymeric form (Figure 3). The polymeric sOPN OD accounted for 86.9±13.1% and 94.2±5.8% in BAL and sputum in all subjects.


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)

Secreted OPN in BAL and sputum.Relative optical density of polymeric, monomeric, and cleaved sOPN in BAL fluid and induced sputum of healthy and asthmatic subjects. White: polymeric sOPN (≥90 kD); light gray: monomeric sOPN (50–55 kD); dark gray: cleaved sOPN (25 kD); black: cleaved sOPN (17 kD).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0025678-g003: Secreted OPN in BAL and sputum.Relative optical density of polymeric, monomeric, and cleaved sOPN in BAL fluid and induced sputum of healthy and asthmatic subjects. White: polymeric sOPN (≥90 kD); light gray: monomeric sOPN (50–55 kD); dark gray: cleaved sOPN (25 kD); black: cleaved sOPN (17 kD).
Mentions: Relative densitometry of the individual BAL and sputum samples from each subject showed that the intensity of the polymeric sOPN bands was much higher relative to the intensity of the other forms of sOPN, suggesting that most of sOPN in BAL and sputum is in polymeric form (Figure 3). The polymeric sOPN OD accounted for 86.9±13.1% and 94.2±5.8% in BAL and sputum in all subjects.

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