Stichtenoth Guido, Jung Philipp, Walter Gabi, Johansson Jan, Robertson Bengt, Curstedt Tore, Herting Egbert
Department of Clinical Chemistry, Laboratory for Surfactant Research, Karolinska Hospital, Sweden.
Pediatr Res. 2006 Mar;59(3):407-11. doi: 10.1203/01.pdr.0000200806.32822.e6.
Pulmonary surfactant is inactivated in meconium aspiration syndrome and neonatal pneumonia. Development of an exogenous surfactant less sensitive to inactivation might be useful for treating these diseases. We investigated in vitro whether addition of the cationic cyclic membrane cross-linking peptide polymyxin B (PxB) and/or calcium chloride (CaCl2) to modified porcine surfactant Curosurf increases resistance to meconium-induced inactivation of surface activity while antimicrobial activity of PxB is maintained. To study bacterial proliferation, Escherichia coli, group B streptococci (GBS), or Staphylococcus aureus were incubated 0-5 h in saline or in meconium in the presence or absence of Curosurf with or without PxB. PxB and CaCl2 improved spreading and adsorption of Curosurf. Curosurf plus CaCl2/PxB needed a 4-fold increase of meconium concentration to increase dynamic surface tension significantly compared with Curosurf plus CaCl2 alone, indicating that PxB further increases the resistance of Curosurf to meconium-induced inactivation. Meconium alone like meconium/Curosurf promoted growth of E. coli and GBS, but addition of Curosurf/PxB or PxB alone significantly reduced the growth of E. coli. Biophysical and antibacterial properties of Curosurf and PxB may be combined into a useful adjunct in the treatment of neonatal Gram-negative pneumonia and/or meconium aspiration syndrome.
肺表面活性物质在胎粪吸入综合征和新生儿肺炎中会失活。开发一种对外源失活不太敏感的表面活性剂可能对治疗这些疾病有用。我们在体外研究了向改良猪表面活性剂珂立苏（Curosurf）中添加阳离子环状膜交联肽多粘菌素B（PxB）和/或氯化钙（CaCl2）是否能增加其对胎粪诱导的表面活性失活的抵抗力，同时保持PxB的抗菌活性。为了研究细菌增殖情况，将大肠杆菌、B族链球菌（GBS）或金黄色葡萄球菌在有或没有珂立苏以及有或没有PxB的情况下，于生理盐水或胎粪中孵育0至5小时。PxB和CaCl2改善了珂立苏的铺展和吸附。与单独使用珂立苏加CaCl2相比，珂立苏加CaCl2/PxB需要将胎粪浓度提高4倍才能显著增加动态表面张力，这表明PxB进一步增强了珂立苏对胎粪诱导失活的抵抗力。单独的胎粪以及胎粪/珂立苏都促进了大肠杆菌和GBS的生长，但添加珂立苏/PxB或单独添加PxB显著降低了大肠杆菌的生长。珂立苏和PxB的生物物理及抗菌特性可结合起来成为治疗新生儿革兰氏阴性肺炎和/或胎粪吸入综合征的有用辅助手段。
