Research

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

Hanna Müller¹ , Caroline End^2,3 , Marcus Renner² , Burkhard M Helmke⁴ , Nikolaus Gassler^4,5 , Christel Weiss⁶ , Dominik Hartl⁷ , Matthias Griese⁷ , Mathias Hafner³ , Annemarie Poustka² , Jan Mollenhauer² and Johannes Poeschl¹

¹  Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany

²  Division of Molecular Genome Analysis, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany

³  Institute of Molecular Biology and Cell Culture Technology, University of Applied Sciences Mannheim, 68163 Mannheim, Germany

⁴  Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany

⁵  Institute of Pathology, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany

⁶  Institute of Medical Statistics and Biomathematics, University Hospital Mannheim, Theodor-Kutzer-Ufer 1, 68135 Mannheim, Germany

⁷  Children's Hospital, University of Munich, Lindwurmstrasse 2a, 80337 Munich, Germany

author email corresponding author email

Respiratory Research 2007, 8:69doi:10.1186/1465-9921-8-69

Published:	1 October 2007

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.