Müller Hanna, End Caroline, Renner Marcus, Helmke Burkhard M, Gassler Nikolaus, Weiss Christel, Hartl Dominik, Griese Matthias, Hafner Mathias, Poustka Annemarie, Mollenhauer Jan, Poeschl Johannes
Division of Neonatology, Department of Pediatrics, University of Heidelberg, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany.
Respir Res. 2007 Oct 1;8(1):69. doi: 10.1186/1465-9921-8-69.
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.
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.
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.
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.
恶性脑肿瘤缺失基因1(DMBT1)是一种分泌型富含半胱氨酸的清道夫受体蛋白,可结合多种细菌,被认为参与肺部先天性宿主防御。我们推测肺部DMBT1可能通过调节表面活性物质功能导致新生儿呼吸窘迫综合征。
采用免疫组织化学和mRNA原位杂交技术,研究患有肺透明膜病的早产和足月新生儿尸检肺组织中DMBT1的表达情况。使用毛细管表面张力仪测定重组人DMBT1对牛和猪表面活性物质功能的影响。采用酶联免疫吸附测定法(ELISA)检测机械通气的早产和足月婴儿气管吸出物中的DMBT1水平。
在呼吸窘迫综合征期间,肺部DMBT1定位于透明膜中。体外将重组人DMBT1添加到表面活性物质中,表面张力呈剂量依赖性增加。根据表面活性物质制剂的不同,添加钙可逆转DMBT1介导的作用。
我们的数据显示,在呼吸窘迫综合征期间,肺部透明膜中有DMBT1表达,并证明DMBT1在体外可增加肺表面张力。这增加了DMBT1可能拮抗呼吸窘迫综合征中表面活性物质补充的可能性,并且可能代表新生儿肺部疾病治疗干预的候选靶分子。