CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D
CRP-ductin, the mouse homologue of gp-340/deleted in malignant brain tumors 1 (DMBT1), binds gram-positive and gram-negative bacteria and interacts with lung surfactant protein D
复制标题
DOI：
10.1002/eji.200323972
复制
发表时间：
2003-08-01
影响因子：
5.4
通讯作者：
Holmskov, U
中科院分区：
文献类型：
--
作者：
Madsen, J;Tornoe, I;Holmskov, U
CRP-ductin是一种主要由小鼠粘膜上皮细胞表达的蛋白质。序列同源性表明，CRP-ductin是人GP-340的小鼠同源物，GP-340是一种糖蛋白，可以凝集微生物并结合肺粘膜集合素表面活性蛋白-D(SP-D)。在此，我们报道了纯化的CRP-ductin以钙依赖的方式与人的SP-D结合，这种结合不被麦芽糖抑制。先前已经观察到SP-D的GP-340结合的相同性质。CRP-ductin对革兰氏阳性和阴性细菌也显示出钙依赖结合。用免疫印迹法检测到抗GP-340的多克隆抗体能与CRP-ductin发生特异性反应。在胰腺外分泌、胃肠道和腮腺导管的上皮细胞中均可见CRP-ductin免疫反应阳性。用逆转录-聚合酶链式反应(RT-PCR)对小鼠组织中的一组RNA样品进行CRP-ductin和SP-D表达的筛选。胰腺是合成CRP-ductin的主要部位，但唾液腺、胃肠道、肝脏、睾丸、子宫和肺也很容易扩增出转录产物。肺是合成SP-D的主要部位，子宫、唾液腺、胸腺、甲状腺、胰腺和睾丸也有转录产物的扩增。我们得出结论，CRP-ductin是人GP-340的小鼠同源物，它与SP-D以及革兰氏阴性和革兰氏阳性细菌的结合能力表明它在粘膜免疫防御中发挥作用。
CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report that purified CRP-ductin binds human SP-D in a calcium-dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp-340 binding of SP-D. CRP-ductin also showed calcium-dependent binding to both gram-positive and -negative bacteria. A polyclonal antibody raised against gp-340 reacted specifically with CRP-ductin in Western blots. Immunoreactivity to CRP-ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP-ductin and SP-D expression by reverse transcription-PCR. The pancreas was the main site of synthesis of CRP-ductin, but transcripts were also readily amplified from salivary gland, the gastrointestinal tract, liver, testis, uterus and lung. Lung was the main site of synthesis of SP-D, but transcripts were also amplified from uterus, salivary gland, thymus, thyroid gland, pancreas and testis. We conclude that CRP-ductin is the mouse homologue of human gp-340 and that its capacity to bind SP-D as well as gram-negative and gram-positive bacteria suggests a role in mucosal immune defense.