Endothelial cell activation promotes foam cell formation by monocytes following transendothelial migration in an in vitro model.
Endothelial cell activation promotes foam cell formation by monocytes following transendothelial migration in an in vitro model.
复制标题
DOI：
10.1016/j.yexmp.2012.03.014
复制
发表时间：
2012-10
影响因子：
3.6
通讯作者：
Muller, William A.
中科院分区：
文献类型：
--
作者：
Westhorpe, Clare L. V.;Dufour, Eric M.;Maisa, Anna;Jaworowski, Anthony;Crowe, Suzanne M.;Muller, William A.
泡沫细胞是存在于动脉粥样硬化的所有阶段的病理特征。泡沫细胞从单核细胞发展而来，单核细胞进入新生的动脉粥样硬化，随后摄取修饰的低密度脂蛋白（LDL）。先前已经使用培养的巨噬细胞喂食修饰的LDL在体外研究了该过程的调节。我们使用我们现有的跨内皮迁移（TEM）的体外模型，以研究这一过程中更生理相关的设置。在我们的模型中，在20%人血清存在下，单核细胞经历TEM穿过原代内皮单层进入底层三维胶原基质。油红O染色法检测泡沫细胞内脂滴。我们证明，在没有额外脂质的情况下，内皮下单核细胞可以在TEM穿过TNF-α激活的内皮的48小时内发育成泡沫细胞。我们的数据表明单核细胞-内皮细胞相互作用和可溶性因子在调节泡沫细胞发育中的作用，包括TNF-α刺激内皮细胞后培养基中脂质的LDL原位氧化。我们的研究提供了一个简单的模型，用于研究体外泡沫细胞发育，模拟体内细胞迁移，并证明炎症在调节早期动脉粥样硬化事件中的关键作用。
Foam cells are a pathological feature present at all stages of atherosclerosis. Foam cells develop from monocytes that enter the nascent atheroma and subsequently ingest modified low density lipoproteins (LDL). The regulation of this process has previously been studied in vitro using cultured macrophages fed modified LDL. We used our existing in vitro model of transendothelial migration (TEM) to study this process in a more physiologically relevant setting. In our model, monocytes undergo TEM across a primary endothelial monolayer into an underlying three-dimensional collagen matrix in the presence of 20% human serum. Foam cells were detected by Oil Red O staining for intracellular lipid droplets. We demonstrate that sub-endothelial monocytes can develop into foam cells within 48 hours of TEM across TNF-α activated endothelium, in the absence of additional lipids. Our data indicate a role for both monocyte-endothelial interactions and soluble factors in the regulation of foam cell development, including oxidation of LDL in situ from lipid present in culture medium following TNF-α stimulation of the endothelial cells. Our study provides a simple model for investigating foam cell development in vitro that mimics cell migration in vivo, and demonstrates the critical role of inflammation in regulating early atherogenic events.
登录
查看更多内容
影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL
DOI：
10.1084/jem.176.3.819
发表时间：
1992-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Muller WA;Weigl SA
通讯作者：
Weigl SA
影响因子：
56.9
作者：
Randolph, GJ;Beaulieu, S;Muller, WA
通讯作者：
Muller, WA
影响因子：
15.9
作者：
Park, Young Mi;Febbraio, Maria;Silverstein, Roy L.
通讯作者：
Silverstein, Roy L.
影响因子：
32.4
作者：
Randolph, GJ;Inaba, K;Muller, WA
通讯作者：
Muller, WA