Enhancement of endotoxin-induced isolated renal tubular cell injury by toxic shock syndrome toxin 1.
Enhancement of endotoxin-induced isolated renal tubular cell injury by toxic shock syndrome toxin 1.
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中毒性休克综合征毒素1增强内毒素诱导的离体肾小管细胞损伤。
DOI：
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发表时间：
1986
影响因子：
6
通讯作者：
P. Peterson
中科院分区：
文献类型：
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作者：
W. Keane;G. Gekker;P. Schlievert;P. Peterson
中毒性休克综合征（TSS）的发病机制尚不清楚。根据实验数据，人们推测葡萄球菌TSS毒素1 （TSST-1）可能与低水平的内毒素协同作用，并导致许多临床表现。我们之前已经证明脂质A，脂多糖（LPS）或内毒素的生物活性成分，诱导离体大鼠肾小管细胞（rtc）的剂量依赖性坏死。在本研究中，作者研究了TSST-1是否会增强这种损伤。通过活体染料排除法评估rtc的生存能力。用1ng /ml的TSST-1或0.1 ng/ml的LPS或脂质A孵育新鲜分离的大鼠rtc，细胞毒性最小（小于6%）。将rtc暴露于1 ng/ml的TSST-1中20分钟，然后清洗，当rtc暴露于0.1 ng/ml的LPS或脂质a时，细胞毒性显著增强。甲胺和氯喹（两种受体介导的内吞作用（RME）抑制剂）可以阻止TSST-1对LPS或脂质a诱导的rtc致敏。2 mM EGTA对细胞外钙的螯合也阻断了TSST-1诱导的RTC对LPS或脂质A的敏化。甲基强的松龙、吲哚美辛、布洛芬和吡利前列素对RTC花生四烯酸代谢的抑制显著抑制了TSST-1和LPS或脂质A诱导的RTC坏死，抑制率为33-62%。改善氧化损伤的硫脲和去铁胺对氧化损伤的抑制作用为34-67%。因此，TSST-1增强了LPS/脂质A的细胞毒性作用，rtc的致敏作用似乎与RME或TSST-1有关。花生四烯酸的氧化代谢和活性氧的产生似乎参与了LPS/脂质a介导的RTC死亡。
The pathogenesis of toxic shock syndrome (TSS) remains unknown. On the basis of experimental data, it has been hypothesized that staphylococcal TSS Toxin 1 (TSST-1) may interact synergistically with low levels of endotoxin and give rise to many of the clinical findings. We have demonstrated previously that lipid A, the biologically active component of lipopolysaccharide (LPS), or endotoxin, induces dose-dependent necrosis of isolated rat renal tubular cells (RTCs). In the present studies, the authors investigated whether this injury could be augmented by TSST-1. The viability of RTCs was assessed by vital dye exclusion. Incubation of freshly isolated rat RTCs with either 1 ng/ml of TSST-1 or 0.1 ng/ml LPS or lipid A had minimal cytotoxicity (less than 6%). Exposure of RTCs to 1 ng/ml TSST-1 for 20 minutes, followed by washing, resulted in a significant enhancement of cytotoxicity when RTCs were exposed to 0.1 ng/ml LPS or lipid A. The sensitization of RTCs by TSST-1 to LPS- or lipid-A-induced injury was prevented by methylamine and chloroquine, two inhibitors of receptor-mediated endocytosis (RME). Chelation of extracellular calcium by 2 mM EGTA also blocked the TSST-1-induced sensitization of RTCs to LPS or lipid A. Inhibition of RTC arachidonic acid metabolism by methylprednisolone, indomethacin, ibuprofen, and piriprost significantly inhibited RTC necrosis induced by TSST-1 and LPS or lipid A by 33-62%. Thiourea and deferoxamine, agents which ameliorate oxidant injury, also inhibited this synergistic injury by 34-67%. Thus, TSST-1 enhanced the cytotoxic effects of LPS/lipid A, and the sensitization of RTCs appeared to involve RME or TSST-1. Oxidative metabolism of arachidonic acid and generation of reactive oxygen species appeared to participate in LPS/lipid-A-mediated RTC death.
肾小管上皮细胞和外植体培养。
影响因子：
--
作者：
Trump,BF;Sato,T;Trifillis,A;Hall-Craggs,M;Kahng,MW;Smith,MW
通讯作者：
Smith,MW
影响因子：
15.9
作者：
PALLER, MS;HOIDAL, JR;FERRIS, TF
通讯作者：
FERRIS, TF