An expanding role for apolipoprotein E in sepsis and inflammation.
An expanding role for apolipoprotein E in sepsis and inflammation.
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DOI：
10.1016/j.amjsurg.2009.10.017
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发表时间：
2010-09
影响因子：
3
通讯作者：
Harris, Hobart W.
中科院分区：
文献类型：
--
作者：
Chuang, Kelley;Elford, Erica L.;Tseng, Jill;Leung, Briana;Harris, Hobart W.
载脂蛋白E（apoE）是血浆脂蛋白的一种成分，在脓毒症中起着重要的作用，但作用不明确。我们已经证明，注射apoE增加了革兰氏阴性细菌脓毒症大鼠模型的脓毒症死亡率，伴随着肝脏自然杀伤T（NKT）细胞的增殖和激活。这种apoE介导的死亡的推测机制是apoE可以结合和运输抗原，推测包括脂多糖（LPS），并促进树突状细胞（DC）的活化，随后NKT活化和细胞因子释放。因此，我们试图证明LPS是导致apoE的存在增强的NKT活化增加的抗原。我们分离了小鼠骨髓来源的DC，用脂质抗原[LPS，阳性对照α-半乳糖神经酰胺（α-GalCer）和异葡萄糖苷3（iGb 3）]加或不加apoE对其进行冲击，然后将DC与杂交瘤NKT共培养。使用ELISA通过白细胞介素-2（IL-2）上清液水平测量NKT活化。在不同浓度的LPS是一个弱刺激NKT激活，无论载脂蛋白E的存在。当存在apoE时，与单独的iGb 3相比，iGb 3（一种内源性配体类似物）引起IL-2应答增加超过两倍（p<0.05）。这些结果表明，内源性配体，而不是LPS，可能是负责NKT激活。类似于iGb 3的分子残基可以作为损伤相关的分子模式，并在脓毒症动物模型中发挥重要作用。
Apolipoprotein E (apoE), a component of plasma lipoproteins, plays an important, but poorly defined role in sepsis. We have shown that injecting apoE increases septic mortality in a rat model of gram-negative bacterial sepsis, with concomitant hepatic natural killer T (NKT) cell proliferation and activation. The presumed mechanism for this apoE-mediated mortality is that apoE can bind and traffic antigens, presumed to include lipopolysaccharide (LPS), and promote activation of dendritic cells (DC) with subsequent NKT activation and cytokine release. Thus, we sought to prove that LPS was the antigen responsible for the increased NKT activation enhanced by the presence of apoE. We isolated murine marrow-derived DCs, pulsed them with lipid antigen [LPS, and positve controls alpha-galactosylceramide (α-GalCer) and isogloboside 3 (iGb3)] with or without apoE, and then co-cultured the DCs with hybridoma NKTs. NKT activation was measured by interleukin-2 (IL-2) supernatant levels using ELISA. LPS at different concentrations was a weak stimulus for NKT activation regardless of apoE presence. When apoE was present, iGb3, an endogenous ligand analog, elicited more than a two-fold increase in IL-2 response when compared to iGb3 alone (p<0.05). These results indicate an endogenous ligand, not LPS, may be responsible for NKT activation. A molecular remnant similar to iGb3 could act as a damage-associated molecular pattern and play a prominent role in animal models of sepsis.
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影响因子：
15.9
作者：
Rensen, PCN;vanOosten, M;vanBerkel, TJC
通讯作者：
vanBerkel, TJC
影响因子：
3.4
作者：
OGISO, M;OHTA, M;KOMOTO, M
通讯作者：
KOMOTO, M
DOI：
10.1073/pnas.0607285104
发表时间：
2007-04-03
影响因子：
11.1
作者：
Speak, Anneliese O.;Salio, Mariolina;Platt, Frances M.
通讯作者：
Platt, Frances M.
影响因子：
64.8
作者：
Mattner, J;DeBord, KL;Bendelac, A
通讯作者：
Bendelac, A
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G