Altered composition of urinary heparan sulfate in patients with COPD.

Lest, Chris H.A. van de; Versteeg, E.M.M.; Veerkamp, J.H.; Berden, Jo H. M.; Born, Jacob van den; Heunks, Leo; Lammers, J.-W. J.; Herwaarden, C L van; Dekhuijzen, P.N.R.; Kuppevelt, A.H.M.S.M. van

doi:10.1164/ajrccm.154.4.8887591

Cited by 12 publications

(12 citation statements)

References 24 publications

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“…The heparan sulfate JM403 epitope, defined by monoclonal antibody JM403 was quantified using an inhibition enzyme immunoassay (EIA) as previously described [7]. The EIA was preceded by urine preparation as described [7].…”

Section: Methodsmentioning

confidence: 99%

“…First, the heparan sulfate specific epitope JM403 was found 10-fold reduced in urine of patients with COPD compared to healthy controls [7]. The decreased urinary content of a specific epitope of heparan sulfate, together with a normal content of heparan sulfate richly present in basement membranes of alveoli suggest a structural alteration or an altered processing of the heparan sulfate molecule in the lungs of patients with emphysema.…”

Section: Introductionmentioning

confidence: 99%

“…The decreased urinary content of a specific epitope of heparan sulfate, together with a normal content of heparan sulfate richly present in basement membranes of alveoli suggest a structural alteration or an altered processing of the heparan sulfate molecule in the lungs of patients with emphysema. In view of the biological functions of heparan sulfate, this could lead to destabilisation of the extracellular matrix, facilitating the development of further proteolytic damage to other matrix components [7]. …”

Section: Introductionmentioning

confidence: 99%

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Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

et al. 2005

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

et al. 2005

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“…Alterations in HS would have consequences for the protective HSPG barrier of the alveolus (7). In the urine of patients with emphysema, a decreased content of the HS epitope JM403 was found together with a normal content of HS (38), suggesting a structural alteration in or an altered processing of HS molecules in the lungs of emphysematous patients. Studies on chemically and enzymatically modified HS indicate that the JM403 epitope contains one or more N-unsubstituted glucosamine and D-glucuronic acid units, and is located in a region of the HS chain composed of mixed N-sulfated and N-acetylated disaccharide units (39).…”

Section: Discussionmentioning

confidence: 96%

Heterogeneity of Heparan Sulfates in Human Lung

Smits¹,

Robbesom²,

Versteeg³

et al. 2004

Am J Respir Cell Mol Biol

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Heparan sulfates (HS), a class of glycosaminoglycans, are long linear complex polysaccharides covalently attached to a protein core. The HS molecules are made up of repeating disaccharides onto which modification patterns are superimposed. This results in a large structural heterogeneity and forms the basis of specific interactions of HS toward a vast array of proteins, including growth factors and proteases. To study HS heterogeneity in the lung, we used phage display technology to select seven antibodies against human lung HS. Antibodies reacted with HS/heparin, but not with other glycosaminoglycans or polyanions. Sulfate groups were essential for antibody binding. The amino acid sequence of the antibodies was established, the complementarity determining region 3 of the heavy chain containing basic amino acids. The antibodies defined HS epitopes with a characteristic tissue distribution. Antibody EV3A1 primarily stained macrophages. Other antibodies primarily stained basement membranes, but with different preference toward type of basement membrane. Antibody EV3C3 was the only antibody which clearly reacted with bronchiolar epithelial cells. In human lung parenchyma, basic fibroblast growth factor and vascular endothelial growth factor were largely bound by HS. Some antibodies blocked a basic fibroblast growth factorbinding site of HS, and one antibody blocked a vascular endothelial growth factor-binding site of heparin. Taken together, these data suggest a specific role for HS epitopes in human lung. The antibodies obtained may be valuable tools to study HS in pulmonary diseases.Heparan sulfates (HS) are members of the glycosaminoglycan (GAG) family, consisting of repeating disaccharide units onto which modification patterns are superimposed. HS bind and modulate a myriad of molecules, including growth factors, cytokines, proteases, antiproteases, matrix molecules, and viral and bacterial proteins (1,2). This large number of interactions suggests an extensive structural variation within HS. The structural diversity of HS is brought about by specific chain modifications during the biosynthesis of HS, including deacetylation, sulfation, and epimerization. The addition of, e.g., sulfate groups leads to the generation of specific motifs that make HS highly versatile, protein-

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“…This assumption may be extended to the hypothesis that GAG in the urine may reflect the turnover of GAG in the glomerulus. Urinary GAG has been suggested as a clinical marker in various diseases, including lupus nephritis [8, 9], urinary bladder damage and bladder tumors [10, 11, 12, 13], mucopolysaccharidoses [14], renal amyloidosis [15], primary glomerulonephritis in experimental animal models and humans [5, 16, 17], proteolytic injury of endothelial and basement membranes which induce capillary leaks in meningococcal septicemia [18], chronic pyelonephritis [19], chronic obstructive pulmonary disease [20], and diabetic nephropathy [21, 22, 23, 24, 25]. An association between heparan sulfate proteoglycan in urine and proteinuria has been reported after renal transplantation [26].…”

Section: Introductionmentioning

confidence: 99%

Isolation, Identification, and Quantitation of Urinary Glycosaminoglycans

Lee

Kim²,

Whang³

et al. 2003

Am J Nephrol

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Background: Substantial amounts of glycosaminoglycans (GAGs) are present in the urine of healthy individuals, but the concentration in the serum is very low. This finding suggests that urinary GAGs come from the glomerulus and may reflect the turnover of GAGs in the glomerulus. Hypothesis: However, little is known about the physiologic regulation of the urinary GAGs in humans, and so investigations are needed to evaluate the effects of age and sex on urinary GAGs in normal individuals. Methods: Eighty-seven healthy subjects were included in this study. Urinary GAGs were isolated and quantified at the nanogram level by combined azure A-silver staining in agarose gels. Results: The level of urinary GAGs peaked at 10–19 years in both sexes. The proportion of chondroitin sulfate decreased with age, but the proportion of heparan sulfate increased with age. Conclusion: The total amount of GAGs and the proportions of chondroitin sulfate, heparan sulfate, and dermatan sulfate appear to change with age. Therefore, investigations in which urinary GAG is used as a parameter of glomerular GAG turnover should ensure that control groups are precisely matched for age. Changes in the proportions of each GAG may be more informative than their absolute levels.

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Altered composition of urinary heparan sulfate in patients with COPD.

Cited by 12 publications

References 24 publications

Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

Short-term variability of biomarkers of proteinase activity in patients with emphysema associated with type Z alpha-1-antitrypsin deficiency

Heterogeneity of Heparan Sulfates in Human Lung

Isolation, Identification, and Quantitation of Urinary Glycosaminoglycans

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