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Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant.

Müller H, End C, Renner M, Helmke BM, Gassler N, Weiss C, Hartl D, Griese M, Hafner M, Poustka A, Mollenhauer J, Poeschl J - Respir. Res. (2007)

Bottom Line: The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer.In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner.The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Hanna.Mueller@med.uni-heidelberg.de

ABSTRACT

Background: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function.

Methods: DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA.

Results: Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation.

Conclusion: Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

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DMBT1 concentration in 1:10 diluted tracheal aspirates of preterm and term infants without correction for epithelial lining fluid dilution. The DMBT1 concentration in 121 tracheal aspirates of 57 ventilated preterm and term infants was analyzed by ELISA using the monoclonal antibody Hyb213-06. The mean DMBT1 concentration was 5.2 ± 1.8 μg/ml. Due to our sampling procedure of tracheal aspirates and due to an additional dilution after sampling, we estimate the volume of epithelial lining fluid in our tracheal aspirates to be at least one-tenth of the recovered volume.
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Figure 5: DMBT1 concentration in 1:10 diluted tracheal aspirates of preterm and term infants without correction for epithelial lining fluid dilution. The DMBT1 concentration in 121 tracheal aspirates of 57 ventilated preterm and term infants was analyzed by ELISA using the monoclonal antibody Hyb213-06. The mean DMBT1 concentration was 5.2 ± 1.8 μg/ml. Due to our sampling procedure of tracheal aspirates and due to an additional dilution after sampling, we estimate the volume of epithelial lining fluid in our tracheal aspirates to be at least one-tenth of the recovered volume.

Mentions: Surfactometer measurements indicate that DMBT1 is able to increase the surface tension of two different surfactant preparations, which would have a negative impact on the treatment of preterm infants. In order so see whether the DMBT1 concentrations used in the in vitro experiments match to the concentrations present in vivo, we analyzed 121 tracheal aspirates (TAs) of 57 preterm and term infants in ELISA (Fig. 5). The 1:10 diluted TAs contained a mean DMBT1 concentration of 5.2 ± 1.8 μg/ml with a lowest DMBT1 concentration of 0.2 μg/ml and a highest of 25 μg/ml, respectively (Fig. 5). In summary 47% of the analyzed tracheal aspirates showed a DMBT1 concentration of more than 15 μg/ml.


Deleted in Malignant Brain Tumors 1 (DMBT1) is present in hyaline membranes and modulates surface tension of surfactant.

Müller H, End C, Renner M, Helmke BM, Gassler N, Weiss C, Hartl D, Griese M, Hafner M, Poustka A, Mollenhauer J, Poeschl J - Respir. Res. (2007)

DMBT1 concentration in 1:10 diluted tracheal aspirates of preterm and term infants without correction for epithelial lining fluid dilution. The DMBT1 concentration in 121 tracheal aspirates of 57 ventilated preterm and term infants was analyzed by ELISA using the monoclonal antibody Hyb213-06. The mean DMBT1 concentration was 5.2 ± 1.8 μg/ml. Due to our sampling procedure of tracheal aspirates and due to an additional dilution after sampling, we estimate the volume of epithelial lining fluid in our tracheal aspirates to be at least one-tenth of the recovered volume.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2164949&req=5

Figure 5: DMBT1 concentration in 1:10 diluted tracheal aspirates of preterm and term infants without correction for epithelial lining fluid dilution. The DMBT1 concentration in 121 tracheal aspirates of 57 ventilated preterm and term infants was analyzed by ELISA using the monoclonal antibody Hyb213-06. The mean DMBT1 concentration was 5.2 ± 1.8 μg/ml. Due to our sampling procedure of tracheal aspirates and due to an additional dilution after sampling, we estimate the volume of epithelial lining fluid in our tracheal aspirates to be at least one-tenth of the recovered volume.
Mentions: Surfactometer measurements indicate that DMBT1 is able to increase the surface tension of two different surfactant preparations, which would have a negative impact on the treatment of preterm infants. In order so see whether the DMBT1 concentrations used in the in vitro experiments match to the concentrations present in vivo, we analyzed 121 tracheal aspirates (TAs) of 57 preterm and term infants in ELISA (Fig. 5). The 1:10 diluted TAs contained a mean DMBT1 concentration of 5.2 ± 1.8 μg/ml with a lowest DMBT1 concentration of 0.2 μg/ml and a highest of 25 μg/ml, respectively (Fig. 5). In summary 47% of the analyzed tracheal aspirates showed a DMBT1 concentration of more than 15 μg/ml.

Bottom Line: The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer.In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner.The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Hanna.Mueller@med.uni-heidelberg.de

ABSTRACT

Background: Deleted in Malignant Brain Tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich protein that binds various bacteria and is thought to participate in innate pulmonary host defense. We hypothesized that pulmonary DMBT1 could contribute to respiratory distress syndrome in neonates by modulating surfactant function.

Methods: DMBT1 expression was studied by immunohistochemistry and mRNA in situ hybridization in post-mortem lungs of preterm and full-term neonates with pulmonary hyaline membranes. The effect of human recombinant DMBT1 on the function of bovine and porcine surfactant was measured by a capillary surfactometer. DMBT1-levels in tracheal aspirates of ventilated preterm and term infants were determined by ELISA.

Results: Pulmonary DMBT1 was localized in hyaline membranes during respiratory distress syndrome. In vitro addition of human recombinant DMBT1 to the surfactants increased surface tension in a dose-dependent manner. The DMBT1-mediated effect was reverted by the addition of calcium depending on the surfactant preparation.

Conclusion: Our data showed pulmonary DMBT1 expression in hyaline membranes during respiratory distress syndrome and demonstrated that DMBT1 increases lung surface tension in vitro. This raises the possibility that DMBT1 could antagonize surfactant supplementation in respiratory distress syndrome and could represent a candidate target molecule for therapeutic intervention in neonatal lung disease.

Show MeSH
Related in: MedlinePlus