The transient pore formed by homologous terminal complement complexes functions as a bidirectional route for the transport of autocrine and paracrine signals across human cell membranes
The transient pore formed by homologous terminal complement complexes functions as a bidirectional route for the transport of autocrine and paracrine signals across human cell membranes
复制标题
DOI：
10.1007/bf03401659
复制
发表时间：
1996-11-01
影响因子：
5.7
通讯作者：
Halperin, JA
中科院分区：
文献类型：
--
作者：
Acosta, JA;Benzaquen, LR;Halperin, JA
背景资料：我们先前已经表明，补体的膜攻击复合物（MAC）刺激细胞增殖，并且将同源MAC插入内皮细胞膜中导致释放有效的有丝分裂原，包括碱性成纤维细胞生长因子（bPGF）。bFGF和其他缺乏信号肽的多肽如白细胞介素1（IL-1）的分泌机制仍然是细胞生物学中的一个悬而未决的问题。我们假设，同源MAC孔本身可以构成一个短暂的路线，用于扩散的生物活性大分子进出的靶cells.Materials和方法：人红细胞鬼和人工脂质囊泡装载标记的生长因子，细胞因子和IgG，并暴露于同源MAC。I-125-大分子的释放随时间变化。在MAC-影响的人红细胞和人脐静脉内皮细胞（HUVEC）中分别测量标记的多肽和荧光葡聚糖（MW：10，000）的掺入。预加载有bFGF、IL-1 β和干扰素-γ（IFN-γ）的α链的红细胞血影在MAC插入时释放多肽，但它们不释放预加载的IgG。受MAC影响的鬼从细胞外介质中吸收放射性IFN-γ。囊泡加载IL-1释放的多肽时，暴露于MAC.Conclusions：同源MAC孔在其nonlytic形式允许出口的胞质蛋白没有信号肽，不通过经典的内质网/高尔基体胞吐途径分泌。我们的研究结果表明，释放，也许是摄取，生物活性大分子通过同源MAC孔是一种新的生物功能的补体系统在哺乳动物中。
Background: We have previously shown that the membrane attack complex (MAC) of complement stimulates cell proliferation and that insertion of homologous MAC into the membranes of endothelial cells results in the release of potent mitogens, including basic fibroblast growth factor (bPGF). The mechanism of secretion of bFGF and other polypeptides devoid of signal peptides, such as interleukin 1 (IL-1) is still an open problem in cell biology. We have hypothesized that the homologous MAC pore itself could constitute a transient route for the diffusion of biologically active macromolecules in and out of the target cells.Materials and Methods: Human red blood cell ghosts and artificial lipid vesicles were loaded with labelled growth factors, cytokines and IgG, and exposed to homologous MAC. The release of the I-125-macromolecules was followed as a function of time. The incorporation of labelled polypeptides and fluorescent dextran (MW:10,000) was measured in MAC-impacted human red blood cells and human umbilical endothelial cells (HUVEC), respectively.Results: Homologous MAC insertion into HUVEC resulted in the massive uptake of 10-kD dextran and induced the release of bFGP, in the absence of any measurable lysis. Red blood cell ghosts preloaded with bFGF, IL-1 beta, and the alpha-chain of interferon-gamma(IFN-gamma) released the polypeptides upon MAC insertion, but they did not release preloaded IgG. MAC-impacted ghosts took up radioactive IFN-gamma from the extracellular medium. Vesicles loaded with IL-1 released the polypeptide when exposed to MAC.Conclusions: The homologous MAC pore in its nonlytic form allows for the export of cytosolic proteins devoid of signal peptides that are not secreted through the classical endoplasmic reticulum/Golgi exocytotic pathways. Our results suggest that the release, and perhaps the uptake, of biologically active macromolecules through the homologous MAC pore is a novel biological function of the complement system in mammals.