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Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism.

Stax MJ, Naarding MA, Tanck MW, Lindquist S, Hernell O, Lyle R, Brandtzaeg P, Eggesbø M, Pollakis G, Paxton WA - PLoS ONE (2011)

Bottom Line: Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions.Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.

Study design: ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions.

Results: DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

Conclusion: The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding.

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Related in: MedlinePlus

DC-SIGN binding is highly variable and correlates with BSSL protein size.(a) Example of a coomassie stained SDS-PAGE separation of breast milk from 7 mothers showing the bile salt-stimulated lipase (BSSL) of variable sizes. (b) Western blot stained with DC-SIGN-Fc of the same 7 milks as depicted in figure a. (c) Breast milks with smaller BSSL protein have stronger DC-SIGN binding capacity than breast milks with larger BSSL protein. Molecular weights (MW) of BSSL protein was compared in milks with strong DC-SIGN binding capacity versus milks with weak DC-SIGN binding capacity. Median protein sizes in the weak and in the strong DC-SIGN binding groups are indicated by a horizontal line.
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pone-0017316-g001: DC-SIGN binding is highly variable and correlates with BSSL protein size.(a) Example of a coomassie stained SDS-PAGE separation of breast milk from 7 mothers showing the bile salt-stimulated lipase (BSSL) of variable sizes. (b) Western blot stained with DC-SIGN-Fc of the same 7 milks as depicted in figure a. (c) Breast milks with smaller BSSL protein have stronger DC-SIGN binding capacity than breast milks with larger BSSL protein. Molecular weights (MW) of BSSL protein was compared in milks with strong DC-SIGN binding capacity versus milks with weak DC-SIGN binding capacity. Median protein sizes in the weak and in the strong DC-SIGN binding groups are indicated by a horizontal line.

Mentions: We have previously identified BSSL from human milk as a strong DC-SIGN binding glycoprotein with variably sized BSSL isoforms differing in their capacity to bind DC-SIGN [15]. We hypothesized that the DC-SIGN binding capacity of BSSL and human milk is correlated with the BSSL protein size. To test this hypothesis, we determined the BSSL protein size and DC-SIGN binding capacity of human milk for 17 mothers from the Netherlands. BSSL protein size was estimated for breast milk separated by SDS-PAGE (figure 1a). The DC-SIGN binding capacity of milk was detected by Western blot (figure 1b) and quantified for all milk samples by ELISA (figure 1c). DC-SIGN binding capacity was highly variable (figure 1b+c) whereas BSSL expression levels were similar in the milks for which BSSL protein size was determined. Although, some milks (not included in this analysis) had decreased BSSL expression levels these cases did not correlate to decreased DC-SIGN binding properties of the corresponding milks. Figures 1a and b represent an example of milks from different mothers with similar BSSL expression levels but variable DC-SIGN binding capacities.


Binding of human milk to pathogen receptor DC-SIGN varies with bile salt-stimulated lipase (BSSL) gene polymorphism.

Stax MJ, Naarding MA, Tanck MW, Lindquist S, Hernell O, Lyle R, Brandtzaeg P, Eggesbø M, Pollakis G, Paxton WA - PLoS ONE (2011)

DC-SIGN binding is highly variable and correlates with BSSL protein size.(a) Example of a coomassie stained SDS-PAGE separation of breast milk from 7 mothers showing the bile salt-stimulated lipase (BSSL) of variable sizes. (b) Western blot stained with DC-SIGN-Fc of the same 7 milks as depicted in figure a. (c) Breast milks with smaller BSSL protein have stronger DC-SIGN binding capacity than breast milks with larger BSSL protein. Molecular weights (MW) of BSSL protein was compared in milks with strong DC-SIGN binding capacity versus milks with weak DC-SIGN binding capacity. Median protein sizes in the weak and in the strong DC-SIGN binding groups are indicated by a horizontal line.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046167&req=5

pone-0017316-g001: DC-SIGN binding is highly variable and correlates with BSSL protein size.(a) Example of a coomassie stained SDS-PAGE separation of breast milk from 7 mothers showing the bile salt-stimulated lipase (BSSL) of variable sizes. (b) Western blot stained with DC-SIGN-Fc of the same 7 milks as depicted in figure a. (c) Breast milks with smaller BSSL protein have stronger DC-SIGN binding capacity than breast milks with larger BSSL protein. Molecular weights (MW) of BSSL protein was compared in milks with strong DC-SIGN binding capacity versus milks with weak DC-SIGN binding capacity. Median protein sizes in the weak and in the strong DC-SIGN binding groups are indicated by a horizontal line.
Mentions: We have previously identified BSSL from human milk as a strong DC-SIGN binding glycoprotein with variably sized BSSL isoforms differing in their capacity to bind DC-SIGN [15]. We hypothesized that the DC-SIGN binding capacity of BSSL and human milk is correlated with the BSSL protein size. To test this hypothesis, we determined the BSSL protein size and DC-SIGN binding capacity of human milk for 17 mothers from the Netherlands. BSSL protein size was estimated for breast milk separated by SDS-PAGE (figure 1a). The DC-SIGN binding capacity of milk was detected by Western blot (figure 1b) and quantified for all milk samples by ELISA (figure 1c). DC-SIGN binding capacity was highly variable (figure 1b+c) whereas BSSL expression levels were similar in the milks for which BSSL protein size was determined. Although, some milks (not included in this analysis) had decreased BSSL expression levels these cases did not correlate to decreased DC-SIGN binding properties of the corresponding milks. Figures 1a and b represent an example of milks from different mothers with similar BSSL expression levels but variable DC-SIGN binding capacities.

Bottom Line: Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions.Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

ABSTRACT

Objective: Dendritic cells bind an array of antigens and DC-SIGN has been postulated to act as a receptor for mucosal pathogen transmission. Bile salt-stimulated lipase (BSSL) from human milk potently binds DC-SIGN and blocks DC-SIGN mediated trans-infection of CD4(+) T-lymphocytes with HIV-1. Objective was to study variation in DC-SIGN binding properties and the relation between DC-SIGN binding capacity of milk and BSSL gene polymorphisms.

Study design: ELISA and PCR were used to study DC-SIGN binding properties and BSSL exon 11 size variation for human milk derived from 269 different mothers distributed over 4 geographical regions.

Results: DC-SIGN binding properties were highly variable for milks derived from different mothers and between samplings from different geographical regions. Differences in DC-SIGN binding were correlated with a genetic polymorphism in BSSL which is related to the number of 11 amino acid repeats at the C-terminus of the protein.

Conclusion: The observed variation in DC-SIGN binding properties among milk samples may have implications for the risk of mucosal transmission of pathogens during breastfeeding.

Show MeSH
Related in: MedlinePlus