Heumann D, Gallay P, Betz-Corradin S, Barras C, Baumgartner J D, Glauser M P
Department of Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Infect Dis. 1993 Jun;167(6):1351-7. doi: 10.1093/infdis/167.6.1351.
The bactericidal/permeability-increasing protein (BPI) inhibits the lipopolysaccharide (LPS)-mediated activation of monocytes. Due to its inhibitory activity for various LPS, BPI has therapeutic potential in endotoxic shock. To be efficient in vivo, BPI should overcome the action of LPS-binding protein (LBP), a serum molecule that increases the expression of LPS-inducible genes via CD14 of monocytes, rBPI23, a recombinant fragment of BPI, prevented in a dose-dependent manner the binding and the internalization of LPS mediated by LBP. Consequently, rBPI23 also inhibited LPS-induced tumor necrosis factor (TNF alpha) synthesis from monocytes. LPS- and LBP-mediated activation of monocytes was totally inhibited when LPS was preincubated with rBPI23. Adding rBPI23 at the same time as LBP resulted in an important but partial inhibition of TNF alpha release, but this inhibition vanished with delaying the time of addition of rBPI23. These studies suggest that the inhibitory activity of BPI is related to its ability to compete with LBP for LPS.
杀菌/通透性增加蛋白（BPI）可抑制脂多糖（LPS）介导的单核细胞激活。由于其对多种LPS具有抑制活性，BPI在内毒素休克中具有治疗潜力。为了在体内发挥有效作用，BPI应克服脂多糖结合蛋白（LBP）的作用，LBP是一种血清分子，可通过单核细胞的CD14增加LPS诱导基因的表达，重组BPI片段rBPI23以剂量依赖的方式阻止了LBP介导的LPS结合和内化。因此，rBPI23也抑制了单核细胞中LPS诱导的肿瘤坏死因子（TNFα）合成。当LPS与rBPI23预孵育时，LPS和LBP介导的单核细胞激活被完全抑制。与LBP同时添加rBPI23会导致TNFα释放受到重要但部分的抑制，但随着rBPI23添加时间的延迟，这种抑制作用消失。这些研究表明，BPI的抑制活性与其与LBP竞争LPS的能力有关。
