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

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.