Lipopolysaccharide Pretreatment Produces Macrophage Endotoxin Tolerance via a Serum-Independent Pathway
作者:
James,
Kraatz Laurel,
Clair Janet,
Bellingham Kyle,
Wahlstrom Jorge L.,
Rodriguez Michael A.,
期刊:
The Journal of Trauma: Injury, Infection, and Critical Care
(OVID Available online 1998)
卷期:
Volume 45,
issue 4
页码: 684-691
ISSN:0022-5282
年代: 1998
出版商: OVID
数据来源: OVID
摘要:
BackgroundLipopolysaccharide activation (LPS2a) 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-kappa B (NF-kappa B) 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-stimulatedTNF 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 LPS (p) in the presence or absence of serum.MethodsMurine peritoneal macrophages were exposed to a range of LPSpconcentrations in the presence or absence of serum. MAPK activation and NF-kappa B were assayed 30 minutes after LPSpstimulation. 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.ResultsIn the presence of serum, 100 ng/mL LPSpactivated MAPK and NF-kappa B, whereas no activation of MAPK or NF-kappa B was seen at this LPSpconcentration in the absence of serum. The absence of serum during 10 ng/mL LPSpdid not prevent LPSp-mediatedinhibition of TNF secretion, and it significantly augmented IL-1 secretion after stimulation with 100 ng/mL LPSain the presence of serum.ConclusionInduction of the alterations in subsequent LPSa-stimulatedcytokine secretion characteristic of endotoxin tolerance by LPSpoccurs via a serum-independent signal transduction pathway.
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