Advanced glycation end products on stored red blood cells increase endothelial reactive oxygen species generation through interaction with receptor for advanced glycation end products.

Advanced glycation end products on stored red blood cells increase endothelial reactive oxygen species generation through interaction with receptor for advanced glycation end products.
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储存的红细胞上的晚期糖基化最终产物通过与受体相互作用以产生晚期糖基化最终产物,从而增加了内皮活性氧的产生。

DOI:
10.1111/j.1537-2995.2010.02689.x
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发表时间:
2010-11
期刊:
影响因子:
2.9
通讯作者:
Lee JS
Lee JS
中科院分区:
医学3区
文献类型:
--
作者:
Mangalmurti NS;Chatterjee S;Cheng G;Andersen E;Mohammed A;Siegel DL;Schmidt AM;Albelda SM;Lee JS

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Recent evidence suggests that storage induced alterations of the red blood cell (RBC) are associated with adverse consequences in susceptible hosts. As RBCs have been shown to form Advanced Glycation Endproducts (AGEs) following increased oxidative stress and under pathologic conditions, we examined whether stored RBCs undergo modification with the specific AGE, N-(Carboxymethyl)lysine (Nε-CML) during standard blood banking conditions. Purified, fresh RBCs from volunteers were compared to stored RBCs (d 35–42 old) obtained from the Blood Bank. Nε-CML formation was quantified using a competitive enzyme-linked immunosorbent assay. The receptor for advanced glycation end-products (RAGE) was detected in human pulmonary microvascular endothelial cells by real-time PCR, western blotting, and flow cytometry. Intracellular reactive oxygen species (ROS) generation was measured by the use of 5-(and 6-)chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester based assays. Stored RBCs showed increased surface Nε-CML formation when compared with fresh RBCs. Human Pulmonary Microvascular Endothelial Cells (HMVEC-L) showed detectable surface RAGE expression constitutively. When compared to fresh RBCs, stored RBCs triggered increased intracellular ROS generation in both Human Umbilical Vein Endothelial Cells (HUVEC) and Human Pulmonary Microvascular Endothelial Cells (HMVEC-L). RBC-induced endothelial ROS generation was attenuated in the presence of soluble RAGE (sRAGE) or RAGE blocking antibody. The formation of the AGE Nε-CML on the surface of stored RBCs is one functional consequence of the storage lesion. AGE-RAGE interactions may be one mechanism by which transfused RBCs cause endothelial cell damage.
DOI: 10.1182/blood-2008-07-166264
发表时间: 2009-01-29
期刊: BLOOD
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