PREVENTION OF LIPOPOLYSACCHARIDE-INDUCED LETHAL TOXICITY BY TYROSINE KINASE INHIBITORS
PREVENTION OF LIPOPOLYSACCHARIDE-INDUCED LETHAL TOXICITY BY TYROSINE KINASE INHIBITORS
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DOI：
10.1126/science.8191285
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发表时间：
1994-05-27
期刊：
影响因子：
56.9
通讯作者：
LEVITZKI, A
中科院分区：
文献类型：
--
作者：
NOVOGRODSKY, A;VANICHKIN, A;LEVITZKI, A
感染性休克是由细菌外膜上的内毒素过度刺激宿主免疫系统，特别是巨噬细胞引起的。Tyrphostin AG 126家族的蛋白酪氨酸激酶抑制剂可保护小鼠免受脂多糖诱导的致死毒性。这种保护作用与这些药物阻止巨噬细胞产生肿瘤坏死因子-α(TNF-α)和一氧化氮的能力有关，也与体内阻断内毒素诱导的肿瘤坏死因子-α的产生有关。此外，这种抑制作用与AG 126阻断脂多糖诱导的小鼠巨噬细胞中p42(MAPK)蛋白底物的酪氨酸磷酸化有关。
Septic shock results from excessive stimulation of the host immune system, especially macrophages, by lipopolysaccharide (LPS), or endotoxin, which resides on the outer membrane of bacteria. Protein tyrosine kinase inhibitors of the tyrphostin AG 126 family protect mice against LPS-induced lethal toxicity. The protection correlates with the ability of these agents to block LPS-induced production of tumor necrosis factor alpha (tNF-alpha) and nitric oxide in macrophages as well as LPS-induced production of TNF-alpha in vivo. Furthermore, this inhibitory effect correlated with the potency of AG 126 to block LPS-induced tyrosine phosphorylation of a p42(MAPK) protein substrate in the murine macrophage.