Stelter F, Witt S, Fürll B, Jack R S, Hartung T, Schütt C
Ernst-Moritz-Arndt-University, Greifswald, Germany.
Eur J Clin Invest. 1998 Mar;28(3):205-13. doi: 10.1046/j.1365-2362.1998.00264.x.
About 50% of septic shock cases are attributed to Gram-negative bacteria or their cell wall compound lipopolysaccharide (LPS, endotoxin). An attractive therapeutic strategy could target the binding of LPS to its cellular receptors. In vitro the soluble form of the endotoxin receptor CD14 (sCD14) competitively prevents binding of LPS to membrane-bound CD14 and inhibits LPS-stimulated macrophage responses.
We tested the in vivo endotoxin-neutralizing capacity of human recombinant sCD14 using a mouse model of shock induced by 8 micrograms g-1 of LPS from Salmonella abortus equi.
In this model, treatment with sCD14 reduced mortality if administered before or simultaneously with LPS. However, application of sCD14 had no effect on the secretion of early proinflammatory cytokines and did not protect the animals against the development of apparent shock symptoms and liver injury. sCD14 also failed to prevent LPS-inducible (7.5 ng g-1) liver injury in galactosamine-sensitized mice.
In line with these findings, sCD14 did not block LPS-induced activation of Kupffer cells in vitro, which might explain why the compound only partially protected in vivo.
约50%的脓毒性休克病例归因于革兰氏阴性菌或其细胞壁成分脂多糖（LPS，内毒素）。一种有吸引力的治疗策略可能是针对LPS与其细胞受体的结合。在体外，内毒素受体CD14的可溶性形式（sCD14）可竞争性地阻止LPS与膜结合型CD14的结合，并抑制LPS刺激的巨噬细胞反应。
我们使用由8微克/克来自马流产沙门氏菌的LPS诱导的休克小鼠模型，测试了重组人sCD14的体内内毒素中和能力。
在该模型中，如果在给予LPS之前或同时给予sCD14，可降低死亡率。然而，应用sCD14对早期促炎细胞因子的分泌没有影响，也不能保护动物免于出现明显的休克症状和肝损伤。sCD14也未能预防半乳糖胺致敏小鼠中LPS诱导的（7.5纳克/克）肝损伤。
根据这些发现，sCD14在体外不能阻断LPS诱导的库普弗细胞活化，这可能解释了该化合物在体内仅提供部分保护的原因。
