脂多糖预处理通过不依赖血清的途径产生巨噬细胞内毒素耐受。

Lipopolysaccharide pretreatment produces macrophage endotoxin tolerance via a serum-independent pathway.

作者信息

Kraatz J, Clair L, Bellingham J, Wahlstrom K, Rodriguez J L, West M A

机构信息

Department of Surgery, Hennepin County Medical Center, University of Minnesota, Minneapolis 55415, USA.

出版信息

J Trauma. 1998 Oct;45(4):684-91. doi: 10.1097/00005373-199810000-00008.

DOI:10.1097/00005373-199810000-00008

PMID:9783605

Abstract

BACKGROUND

Lipopolysaccharide activation (LPSa) of macrophages is thought to occur via a CD14-dependent mechanism with a requirement for the serum factor, lipopolysaccharide binding protein. LPS-stimulated, CD14-dependent signal transduction is associated with phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor-kappaB (NF-kappaB) translocation, and secretion of tumor necrosis factor (TNF) and interleukin-1 (IL-1). Macrophage endotoxin tolerance after low-dose LPS pretreatment (LPSp) is characterized by inhibition of LPSa-stimulated TNF and augmentation of IL-1 secretion. We sought to determine the role of CD14-dependent pathways in the induction of endotoxin tolerance by comparing the effects of LPSp in the presence or absence of serum.

METHODS

Murine peritoneal macrophages were exposed to a range of LPSp concentrations in the presence or absence of serum. MAPK activation and NF-kappaB were assayed 30 minutes after LPSp stimulation. TNF production and IL-1 were measured 6 hours after stimulation with 100 ng/mL LPSa, with or without 24-hour 10 ng/mL LPSp.

RESULTS

In the presence of serum, 100 ng/mL LPSp activated MAPK and NF-kappaB, whereas no activation of MAPK or NF-kappaB was seen at this LPSp concentration in the absence of serum. The absence of serum during 10 ng/mL LPSp did not prevent LPSp-mediated inhibition of TNF secretion, and it significantly augmented IL-1 secretion after stimulation with 100 ng/mL LPSa in the presence of serum.

CONCLUSION

Induction of the alterations in subsequent LPSa-stimulated cytokine secretion characteristic of endotoxin tolerance by LPSp occurs via a serum-independent signal transduction pathway.

摘要

背景

巨噬细胞的脂多糖激活（LPSa）被认为是通过一种依赖CD14的机制发生的，需要血清因子脂多糖结合蛋白的参与。脂多糖刺激的、依赖CD14的信号转导与丝裂原活化蛋白激酶（MAPK）的磷酸化、核因子κB（NF-κB）的易位以及肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）的分泌有关。低剂量脂多糖预处理（LPSp）后的巨噬细胞内毒素耐受的特征是抑制LPSa刺激的TNF分泌并增强IL-1的分泌。我们试图通过比较有血清和无血清情况下LPSp的作用来确定依赖CD14的信号通路在内毒素耐受诱导中的作用。

方法

在有血清或无血清的情况下，将小鼠腹腔巨噬细胞暴露于一系列LPSp浓度。LPSp刺激30分钟后检测MAPK激活和NF-κB。在用100 ng/mL LPSa刺激6小时后，测量TNF产生和IL-1水平，刺激时有无24小时10 ng/mL LPSp预处理。

结果

在有血清的情况下，100 ng/mL LPSp激活了MAPK和NF-κB，而在无血清时，此LPSp浓度下未观察到MAPK或NF-κB的激活。在10 ng/mL LPSp处理期间无血清并不妨碍LPSp介导的TNF分泌抑制，并且在有血清的情况下，在用100 ng/mL LPSa刺激后显著增强了IL-1的分泌。