Varsano S, Frolkis I, Shapiro H, Ophir D
Department of Pulmonary Medicine, Sapir Medical Center, Meir General Hospital, Kfar Sava, Isreal.
Laryngoscope. 1996 May;106(5 Pt 1):599-604. doi: 10.1097/00005537-199605000-00015.
Recent evidence suggests that complement is activated in human nasal airways in inflammatory states. Activated complement protects the nasal mucosa against microorganisms, but also has the potential to lyse the host's normal cells. Complement-mediated cell lysis depends on adsorption of complement to the cell membrane and on uninterrupted activation of the complement cascade upon the same cell membrane. In the present study, the authors investigated first whether key complement components, C3-related fragments, are adsorbed to nasal epithelial cell membrane. Second, we investigated whether nasal epithelium expresses cell membrane complement regulatory proteins that are known as interruptors of complement activation. Studies were done using fresh nasal mucosa obtained at turbinectomies from allergic rhinitis and vasomotor rhinitis patients. In addition, in order to establish an in vitro model, studies were also done using primary cell cultures of nasal epithelium. We have found that complement C3-related fragments are present on cell membranes of fresh nasal epithelium and that C3-related fragments are adsorbed to the epithelial cell membrane in nasal mucosa tissue segments and in cell cultures that were incubated with autologous serum. Adsorption of C3-related fragments to the cell membrane of cultured nasal epithelial cells was found by flow cytometry analysis to be concentration-dependent. In addition, we found that nasal epithelium in fresh tissue and in cell culture express three cell membrane complement regulatory proteins: membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and CD59. Our findings in fresh nasal epithelium suggest that complement activation may occur upon the nasal epithelial cell membrane during inflammation in vivo and that nasal epithelium might regulate this complement activation. Our in vitro cell culture model will allow further investigations of complement activation and regulation upon the human nasal epithelial cell membrane.
最近的证据表明，在炎症状态下人体鼻气道中的补体被激活。激活的补体可保护鼻黏膜免受微生物侵害，但也有可能裂解宿主的正常细胞。补体介导的细胞裂解取决于补体在细胞膜上的吸附以及在同一细胞膜上补体级联反应的持续激活。在本研究中，作者首先研究关键补体成分、C3相关片段是否吸附于鼻上皮细胞膜。其次，我们研究鼻上皮是否表达作为补体激活中断因子的细胞膜补体调节蛋白。研究使用了从变应性鼻炎和血管运动性鼻炎患者鼻甲切除术中获取的新鲜鼻黏膜。此外，为建立体外模型，还使用了鼻上皮原代细胞培养进行研究。我们发现新鲜鼻上皮细胞膜上存在补体C3相关片段，并且在鼻黏膜组织切片以及与自体血清孵育的细胞培养物中，C3相关片段吸附于上皮细胞膜。通过流式细胞术分析发现，C3相关片段在培养的鼻上皮细胞膜上的吸附呈浓度依赖性。此外，我们发现新鲜组织和细胞培养中的鼻上皮表达三种细胞膜补体调节蛋白：膜辅因子蛋白（MCP，CD46）、衰变加速因子（DAF，CD55）和CD59。我们在新鲜鼻上皮中的发现表明，在体内炎症过程中补体激活可能发生于鼻上皮细胞膜上，并且鼻上皮可能调节这种补体激活。我们的体外细胞培养模型将有助于进一步研究人鼻上皮细胞膜上的补体激活和调节。
