Apolipoprotein A-I diminishes acute lung injury and sepsis in mice induced by lipoteichoic acid
Apolipoprotein A-I diminishes acute lung injury and sepsis in mice induced by lipoteichoic acid
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DOI：
10.1016/j.cyto.2008.04.002
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发表时间：
2008-07-01
期刊：
影响因子：
3.8
通讯作者：
Wu, Man-Ping
中科院分区：
文献类型：
--
作者：
Jiao, Yan-ling;Wu, Man-Ping
脂磷壁酸（LTA）作为主要的免疫刺激物，触发全身炎症反应。我们的假设是ApoA-I可以中和LTA毒性，就像它对LPS的作用一样。用LTA攻击BALB/c小鼠，然后施用人ApoA-I。我们发现ApoA-I可以减轻LTA诱导的急性肺损伤和炎症，并显著抑制LTA诱导的血清中IL-1 β和TNF-α的积聚（分别为P < 0.01和P < 0.05），以及支气管肺泡灌洗液（BAL）中IL-1 β和TNF-α的积聚（分别为P < 0.01和P < 0.05）。ApoA-I能显著降低LTA激活的巨噬细胞对L-929细胞的杀伤作用，且呈剂量依赖性。此外，ApoA-I处理可以减少巨噬细胞中LTA介导的NFB κ核转位。体外结合试验表明ApoA-I可与LTA结合。这些结果清楚地表明，ApoA-I可以有效地防止LTA诱导的脓毒症和急性肺损伤。其作用机制可能与LTA的结合和中和作用有关。(C)2008爱思唯尔有限公司保留所有权利。
Lipoteichoic acid (LTA), as a primary immunostimulus, triggers the systematic inflammatory responses. Our hypothesis is that ApoA-I can neutralize LTA toxicity, like its effect on LPS. BALB/c mice were challenged with LTA, followed by human ApoA-I administration. We found that ApoA-I could attenuate LTA-induced acute lung injury and inflammation and significantly inhibit LTA-induced IL-1 beta and TNF-alpha accumulation in the serum (P < 0.01 and P < 0.05, respectively), as well as in bronchoalveolar lavage (BAL) fluid (P < 0.01 and P < 0.05, respectively). Moreover, ApoA-I could significantly reduce the L-929 cell mortality caused by LTA-activated macrophages in a dose-dependent fashion. Furthermore, ApoA-I treatment could diminish LTA-mediated NFB kappa nuclear translocation in macrophages. An in vitro binding assay indicated that ApoA-I can bind LTA. These results clearly indicated that ApoA-I can effectively protect against LTA-induced sepsis and acute lung damage. The mechanism might be related to the binding and neutralization of LTA. (C) 2008 Elsevier Ltd. All rights reserved.