Janér Joakim, Lassus Patrik, Haglund Caj, Paavonen Karri, Alitalo Kari, Andersson Sture
Hospital for Children and Adolescents, Department of Surgery, Helsinki University Central Hospital, and Molecular/Cancer Biology Laboratory and Ludwig Institute for Cancer Research, University of Helsinki, Helsinki, Finland.
Am J Respir Crit Care Med. 2006 Aug 1;174(3):326-30. doi: 10.1164/rccm.200508-1291OC. Epub 2006 May 11.
In mice, vascular endothelial growth factor-C (VEGF-C) plays an important role in development of the lymphatic system and in pathogenesis of pulmonary inflammation. Its role in development of the lymphatic system in human lung and in lung injury in newborns remains unclear.
We studied the role of VEGF-C in developing human lung, and in acute and chronic lung injury in preterm infants.
Included in the immunohistochemistry study were 10 fetuses, 15 control neonates without primary lung disease, 15 preterm infants with respiratory distress syndrome, and 8 infants with bronchopulmonary dysplasia. Tracheal aspirate fluid samples of intubated very-low-birth-weight infants during Postnatal Weeks 1-5 were analyzed with ELISA.
Bronchiolar staining for VEGF-C was observed in all 48 samples. Alveolar epithelial staining was seen in most fetuses (8/10). In addition, staining was observed in alveolar macrophages in bronchopulmonary dysplasia (4/8), and late respiratory distress syndrome (2/7). VEGF receptor-3 (VEGFR-3) staining was observed in lymphatic endothelium adjacent to vascular endothelium. VEGF-C was expressed consistently in tracheal aspirate fluid, being highest during the first 2 postnatal days. Antenatal administration of glucocorticoids was associated with higher VEGF-C in tracheal aspirate fluid.
The pattern of pulmonary VEGF-C and VEGFR-3 protein expression and consistent VEGF-C protein appearance in tracheal aspirate fluid in human preterm infants indicate a role for VEGF-C in the physiologic development of the lymphatic system of the lung.
在小鼠中，血管内皮生长因子 -C（VEGF -C）在淋巴系统发育和肺部炎症发病机制中起重要作用。其在人类肺部淋巴系统发育及新生儿肺损伤中的作用尚不清楚。
我们研究了VEGF -C在人类肺发育以及早产儿急性和慢性肺损伤中的作用。
免疫组织化学研究纳入了10例胎儿、15例无原发性肺部疾病的对照新生儿、15例患有呼吸窘迫综合征的早产儿以及8例患有支气管肺发育不良的婴儿。对出生后第1 - 5周期间气管插管的极低出生体重婴儿的气管吸出液样本进行酶联免疫吸附测定（ELISA）分析。
在所有48个样本中均观察到细支气管VEGF -C染色。在大多数胎儿（8/10）中可见肺泡上皮染色。此外，在支气管肺发育不良（4/8）和晚期呼吸窘迫综合征（2/7）的肺泡巨噬细胞中也观察到染色。在与血管内皮相邻的淋巴管内皮中观察到VEGF受体 -3（VEGFR -3）染色。VEGF -C在气管吸出液中持续表达，在出生后的头两天最高。产前给予糖皮质激素与气管吸出液中较高的VEGF -C有关。
人类早产儿肺部VEGF -C和VEGFR -3蛋白表达模式以及气管吸出液中持续出现的VEGF -C蛋白表明VEGF -C在肺淋巴系统的生理发育中起作用。
