Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells.
Effects of Aggregatibacter actinomycetemcomitans leukotoxin on endothelial cells.
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DOI：
10.1016/j.micpath.2013.05.001
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发表时间：
2013-08
影响因子：
3.8
通讯作者：
Grau, Georges E.
中科院分区：
文献类型：
--
作者：
Dietmann, Anelia;Millonig, Alban;Combes, Valery;Couraud, Pierre-Olivier;Kachlany, Scott C.;Grau, Georges E.
伴放线聚集杆菌是一种产生白细胞毒素（LtxA）的人类病原体，其是主要的毒力因子。在这项研究中，LtxA对微血管内皮细胞活力和表型的影响进行了研究。如分别通过四唑盐和膜联蛋白V测定所评估的，高剂量的单次LtxA处理（500 ng/ml至5 μg/ml）显著且不可逆地降低细胞增殖并诱导细胞凋亡。泛半胱天冬酶抑制剂z-VAD-fmk部分抑制细胞凋亡。LtxA作用72 h后细胞周期阻滞于G2/M期。在500 ng/ml和5 μg/ml之间，在长期或短期刺激后，LtxA增加ICAM-1和VCAM-1的表达，以及表达这些粘附分子的内皮细胞的百分比。因此，伴放线菌LtxA通过上调ICAM-1和VCAM-1对人脑内皮细胞具有显著的促炎作用。高浓度的LtxA可抑制微血管内皮细胞的增殖并诱导其凋亡。LtxA对内皮细胞具有抗增殖作用。LtxA诱导内皮细胞G2/M期细胞周期阻滞。LtxA诱导内皮细胞凋亡。LtxA可增加内皮细胞ICAM-1和VCAM-1的表达。
Aggregatibacter actinomycetemcomitans is a human pathogen that produces leukotoxin (LtxA) as a major virulence factor. In this study the effect of LtxA on microvascular endothelial cell viability and phenotype was studied. High doses of single LtxA treatment (500 ng/ml to 5 μg/ml) significantly and irreversibly decreased cell proliferation and induced apoptosis, as assessed by tetrazolium salt and annexin V assay, respectively. Apoptosis was partially inhibited by the pan-caspase inhibitor, z-VAD-fmk. LtxA caused a cell cycle arrest in the G2/M phase after 72 h. Between 500 ng/ml and 5 μg/ml, after long- or short-term stimulation LtxA increased the expression of ICAM-1 and VCAM-1, as well as the percentages of endothelial cells expressing these adhesion molecules. Thus, A. actinomycetemcomitans LtxA has substantial pro-inflammatory effects on human brain endothelial cells by upregulation of ICAM-1 and VCAM-1. Furthermore, LtxA in higher concentration was found to decrease proliferation and induces apoptosis in microvascular endothelial cells. LtxA has anti-proliferative effects on endothelial cells. LtxA induces a G2/M phase cell cycle arrest in endothelial cells. LtxA induces apoptosis in endothelial cells. LtxA increased expression of ICAM-1 and VCAM-1 in endothelial cells.
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DOI：
10.1083/jcb.111.3.1233
发表时间：
1990-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kramer RH;Cheng YF;Clyman R
通讯作者：
Clyman R
影响因子：
4.8
作者：
Lally, ET;Kieba, IR;Billings, PC
通讯作者：
Billings, PC
影响因子：
2.7
作者：
Kachlany, Scott C.;Schwartz, Amy B.;Rao, Jia
通讯作者：
Rao, Jia
影响因子：
3.4
作者：
Kieba, Irene R.;Fong, Karen P.;Lally, Edward T.
通讯作者：
Lally, Edward T.
影响因子：
4.1
作者：
Kelk, Peyman;Claesson, Rolf;Johansson, Anders
通讯作者：
Johansson, Anders