Shin M L, Hänsch G, Mayer M M
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2522-5. doi: 10.1073/pnas.78.4.2522.
To evaluate the effect of membrane lipid acyl-chain packing on the efficiency of cell lysis by complement, we have studied membrane modulation by 2-(2-methoxy)-ethoxyethyl-8-(cis-2-n-octylcyclopropyl)-octanoate (A2C) and by myristoleyl alcohol, the cis isomer of a C14:1 aliphatic alcohol. These substances are known to increase the membrane lipid disorder by virtue of the bend in their acyl chains, which is believed to loosen the phospholipid acyl-chain packing. We have found that both of these compounds markedly enhance the lysis of erythrocytes by the terminal complement proteins C5b-9. The enhancing effect by A2C is operative in the formation of erythrocytes carrying complement components C5b, C6, and C7, as well as in the subsequent reactions with complement components C8 and C9. We have also found that A2C-treated erythrocytes bind C5b6 to a measurable extent, whereas untreated erythrocytes do not. We attribute this to a shift in the partition equilibrium of C5b6 toward membrane association, which would improve lytic efficiency. The increase of membrane lipid disorder by these agents would also be expected to increase insertion of hydrophobic peptides from C7, C8, and C9, with consequent gain in lytic efficiency. Treatment of erythrocytes with sublytic doses of NaDodSO4, or Triton X-100 did not enhance lysis by C5b-9 appreciably, suggesting that enhancement of lysis by C5b-9 is not a general property of amphiphiles.
为了评估膜脂酰基链堆积对补体介导的细胞裂解效率的影响，我们研究了2-(2-甲氧基)-乙氧基乙基-8-(顺式-2-正辛基环丙基)-辛酸酯(A2C)和肉豆蔻油酸醇（一种C14:1脂肪醇的顺式异构体）对膜的调节作用。已知这些物质因其酰基链的弯曲而增加膜脂无序性，据信这会使磷脂酰基链堆积松弛。我们发现，这两种化合物均能显著增强终末补体蛋白C5b-9介导的红细胞裂解。A2C的增强作用在携带补体成分C5b、C6和C7的红细胞形成过程中以及随后与补体成分C8和C9的反应中均起作用。我们还发现，经A2C处理的红细胞能在一定程度上结合C5b6，而未处理的红细胞则不能。我们将此归因于C5b6分配平衡向膜结合方向的转变，这将提高裂解效率。这些试剂引起的膜脂无序性增加也有望增加C7、C8和C9中疏水肽的插入，从而提高裂解效率。用亚裂解剂量的十二烷基硫酸钠(NaDodSO4)或 Triton X-100处理红细胞并不能明显增强C5b-9介导的裂解，这表明C5b-9介导的裂解增强不是两亲性分子的普遍特性。
