Varsano S, Frolkis I, Rashkovsky L, Ophir D, Fishelson Z
Department of Pulmonary Medicine, Meir General Hospital, Tel-Aviv, Israel.
Am J Respir Cell Mol Biol. 1996 Dec;15(6):731-7. doi: 10.1165/ajrcmb.15.6.8969267.
Complement in the respiratory tract protects the host from invading micoorganisms and other inhaled insults, but may damage normal tissue. Recently we reported that human respiratory epithelium from the nose to the alveoli expresses three cell-membrane regulators of complement activation: membrane cofactor protein (MCP, CD46), decay accelerating factor (DAF; CD55), and CD59. In this study we investigated whether two of these complement-regulatory proteins, DAF and CD59, protect human nasal epithelial cells from complement-mediated lysis. Treatment of nasal epithelial cells in suspension with 50% or 100% normal human serum (NHS) lysed small percentages of cells (8% and 16%, respectively). Addition of complement activators, rabbit serum antinasal epithelial cells (anti-NEC), or lipopolysaccharide (LPS) increased cell lysis in the presence of 50% NHS in a dose-dependent manner up to 50% and 35% lysis, respectively. Human serum deficient in C3 or C7 did not lyse nasal epithelial cells even in the presence of anti-NEC. To assay the contribution of DAF and CD59 to cell protection against lysis, nasal epithelial cells in suspension were treated with appropriate blocking antibodies. Both anti-DAF and anti-CD59 markedly increased the susceptibility of human nasal epithelial cells to lysis by complement. At 50% NHS, anti-DAF and anti-CD59 antibodies increased epithelial cell lysis from 8% to 24% and 67%, respectively. A similar pattern of response to complement was demonstrated by monolayers of substrate-anchored cultured cells. These results indicate that DAF and CD59 protect human nasal epithelial cells from complement-mediated lysis; however, intense activation of complement may overcome this protection, leading to cell death and tissue injury. We speculate that imbalance between complement regulation and complement activation in the human respiratory tract in disease may result in tissue injury and impaired tissue function.
呼吸道中的补体可保护宿主免受入侵微生物及其他吸入性侵害，但也可能损害正常组织。最近我们报道，从鼻腔到肺泡的人类呼吸道上皮表达三种补体激活的细胞膜调节因子：膜辅因子蛋白（MCP，CD46）、衰变加速因子（DAF；CD55）和CD59。在本研究中，我们调查了这两种补体调节蛋白DAF和CD59是否能保护人类鼻上皮细胞免受补体介导的溶解。用50%或100%正常人血清（NHS）处理悬浮的鼻上皮细胞，导致少量细胞溶解（分别为8%和16%）。添加补体激活剂、兔抗鼻上皮细胞血清（抗-NEC）或脂多糖（LPS），在50%NHS存在的情况下，以剂量依赖方式增加细胞溶解，分别高达50%和35%。缺乏C3或C7的人血清即使在存在抗-NEC的情况下也不会溶解鼻上皮细胞。为了测定DAF和CD59对细胞抗溶解保护作用的贡献，用适当的阻断抗体处理悬浮的鼻上皮细胞。抗DAF和抗CD59均显著增加了人类鼻上皮细胞对补体溶解的敏感性。在50%NHS时，抗DAF和抗CD59抗体分别将上皮细胞溶解率从8%提高到24%和67%。底物锚定培养细胞的单层对补体的反应模式相似。这些结果表明，DAF和CD59可保护人类鼻上皮细胞免受补体介导的溶解；然而，补体的强烈激活可能会克服这种保护作用，导致细胞死亡和组织损伤。我们推测，疾病状态下人类呼吸道中补体调节与补体激活之间的失衡可能导致组织损伤和组织功能受损。
