Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo.
Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo.
复制标题
体内氧化修饰的低密度脂蛋白对白细胞粘附的超氧化物依赖性刺激。
DOI：
10.1161/01.atv.12.7.824
复制
发表时间：
1992
期刊：
影响因子：
--
通讯作者：
K. Messmer
中科院分区：
文献类型：
--
作者：
H. Lehr;M. Becker;S. Marklund;Christoph Hubner;K. Arfors;A. Kohlschutter;K. Messmer
氧化修饰的低密度脂蛋白（Ox-LDL）导致白细胞粘附于内皮，这是早期动脉粥样硬化形成中常见的特征。由于白细胞粘附在各种病理生理条件下涉及超氧化物的产生，我们探讨了超氧化物同样参与白细胞粘附响应Ox-LDL的可能性。在我们的研究中，我们使用背侧皮褶室模型对仓鼠白细胞与内皮细胞的相互作用进行活体显微镜观察。我们在这里表明，注射人LDL（4毫克/公斤LDL胆固醇氧化修饰的7.5 μ M铜2+在37 ℃孵育18小时）引起对照仓鼠（n = 7）滚动和粘附循环白细胞沿着内皮的小动脉和毛细血管后微静脉。当用牛铜锌超氧化物歧化酶（CuZn-SOD，0.25 mg/kg，n = 7）或肝素（2，000 IU/kg，n = 7）预处理仓鼠时，这种粘附显著减弱。CuZn-SOD输注和肝素诱导的细胞外SOD从内皮细胞表面释放到血浆，导致血浆SOD活性几乎相等。再增加CuZn-SOD的剂量至5 mg/kg（n = 6）不能进一步抑制Ox-LDL诱导的白细胞粘附。用灭活的CuZn-SOD预处理仓鼠没有效果。这些结果表明，Ox-LDL刺激白细胞粘附通过一个超氧化物依赖的步骤，他们指出了一种可能的机制，抗氧化剂可能会抑制实验和临床动脉粥样硬化的发病。
Low density lipoprotein modified by oxidation (Ox-LDL) causes adhesion of leukocytes to the endothelium, a feature common in early atherogenesis. Because leukocyte adhesion under various pathophysiological conditions involves superoxide generation, we explored the possibility that superoxide is likewise involved in leukocyte adhesion in response to Ox-LDL. For our studies, we used the dorsal skin fold chamber model for intravital microscopic observation of leukocyte-endothelium interactions in hamsters. We show here that injection of human LDL (4 mg/kg LDL cholesterol oxidatively modified by incubation in 7.5 microM Cu2+ for 18 hours at 37 degrees C) elicited in control hamsters (n = 7) the rolling and adhesion of circulating leukocytes along the endothelium of arterioles and postcapillary venules. This adhesion was significantly attenuated when hamsters were pretreated with bovine copper-zinc-superoxide dismutase (CuZn-SOD, 0.25 mg/kg, n = 7) or heparin (2,000 IU/kg, n = 7). The CuZn-SOD infusion and the heparin-induced release of extracellular SOD from endothelial cell surfaces to plasma resulted in nearly equal plasma SOD activities. Further inhibition of Ox-LDL-induced leukocyte adhesion could not be achieved by increasing the dose of CuZn-SOD to 5 mg/kg (n = 6). Pretreatment of the hamsters with inactivated CuZn-SOD showed no effect. These results indicate that Ox-LDL stimulates leukocyte adhesion through a superoxide-dependent step, and they indicate a possible mechanism by which antioxidants might inhibit the onset of experimental and clinical atherosclerosis.
登录
查看更多内容
DOI：
10.1073/pnas.86.4.1372
发表时间：
1989-02-01
影响因子：
11.1
作者：
PALINSKI, W;ROSENFELD, ME;WITZTUM, JL
通讯作者：
WITZTUM, JL
影响因子：
20.3
作者：
S. Hamburger;R. McEver
通讯作者：
S. Hamburger;R. McEver
DOI：
10.1073/pnas.85.8.2805
发表时间：
1988-04-01
影响因子：
11.1
作者：
QUINN, MT;PARTHASARATHY, S;STEINBERG, D
通讯作者：
STEINBERG, D
影响因子：
15.9
作者：
PARTHASARATHY, S;YOUNG, SG;STEINBERG, D
通讯作者：
STEINBERG, D
DOI：
10.1073/pnas.81.12.3883
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
STEINBRECHER, UP;PARTHASARATHY, S;STEINBERG, D
通讯作者：
STEINBERG, D