Erpenbeck Veit J, Fischer Ina, Wiese Kathrin, Schaumann Frank, Schmiedl Andreas, Nassenstein Christina, Krug Norbert, Hohlfeld Jens M
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Int Arch Allergy Immunol. 2009;149(4):333-42. doi: 10.1159/000205579. Epub 2009 Mar 17.
There is increasing interest in testing surfactant preparations for asthma therapy. Previously, Curosurf was demonstrated to increase inflammation in allergic asthmatics. So far, little is known about the immunomodulatory effects of therapeutic surfactants, in particular concerning the interaction of surfactant components with eosinophils as key effector cells of the allergic airway inflammation. The aim of the present study was to determine the effect of different therapeutic surfactants on cellular functions of eosinophils.
Eosinophils were isolated from peripheral blood of atopic volunteers and incubated with the natural animal-derived surfactants Curosurf or Alveofact or the synthetic recombinant human surfactant Venticute at different concentrations for up to 42 h.
Curosurf and Venticute modulated the viability of eosinophils. While incubation with Curosurf increased the number of necrotic eosinophils after 1, 20 and 42 h, Venticute increased the number of apoptotic and necrotic cells after 1 h, but there were no differences compared with control cells at later time points. All surfactant preparations increased the levels of eosinophil cationic protein after 20 h and, in addition, Curosurf enhanced eosinophil cationic protein release after 42 h. The supernatant of eosinophils induced chemotaxis against autologous eosinophils, and the presence of Curosurf, but not Alveofact or Venticute, augmented the chemotactic effect. Chemotaxis was partly blocked by inhibition of eotaxin but not by inhibition of leukotrienes or platelet-activating factor.
Therapeutic surfactants differ in their effects on eosinophil viability and the accompanying release of inflammatory mediators and chemotactic signals. Proinflammatory effects were most pronounced for the natural surfactant Curosurf.
测试用于哮喘治疗的表面活性剂制剂的兴趣日益增加。此前,已证明珂立苏可增加过敏性哮喘患者的炎症。到目前为止,关于治疗性表面活性剂的免疫调节作用知之甚少,尤其是表面活性剂成分与作为过敏性气道炎症关键效应细胞的嗜酸性粒细胞之间的相互作用。本研究的目的是确定不同治疗性表面活性剂对嗜酸性粒细胞细胞功能的影响。
从特应性志愿者的外周血中分离嗜酸性粒细胞,并与不同浓度的天然动物源性表面活性剂珂立苏或肺泡表面活性物质,或合成重组人表面活性剂文适进行孵育,长达42小时。
珂立苏和文适调节了嗜酸性粒细胞的活力。与珂立苏孵育1、20和42小时后,坏死嗜酸性粒细胞数量增加,而文适在1小时后增加了凋亡和坏死细胞的数量,但在随后的时间点与对照细胞相比没有差异。所有表面活性剂制剂在20小时后均增加了嗜酸性粒细胞阳离子蛋白水平,此外,珂立苏在42小时后增强了嗜酸性粒细胞阳离子蛋白的释放。嗜酸性粒细胞的上清液诱导针对自体嗜酸性粒细胞的趋化性,并且珂立苏的存在增强了趋化作用,而肺泡表面活性物质或文适则没有。趋化作用部分被嗜酸性粒细胞趋化因子的抑制所阻断,但未被白三烯或血小板活化因子的抑制所阻断。
治疗性表面活性剂对嗜酸性粒细胞活力以及伴随的炎症介质和趋化信号释放的影响各不相同。天然表面活性剂珂立苏的促炎作用最为明显。