Chylomicrons combined with endotoxin moderate microvascular permeability:

Innate Immunity

Austin L.Spitzer¹ 

关键词: endothelium;    chylomicron;    tumor necorosis factor-α;    platelet activating factor;    hydraulic conductivity;   

DOI  :  10.1177/1753425910369849

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

Triglyceride-rich lipoprotein-bound endotoxin (CM-LPS) inhibits the host innate immune response to sepsis by attenuating the hepatocellular response to pro-inflammatory cytokine stimulation. This ‘cytokine tolerance’ in hepatocytes is a transient, receptor-dependent process that correlates with internalization of CM-LPS via low density lipoprotein (LDL) receptors. Since endothelial cells are integral to the immune response and similarly express LDL receptors, we hypothesized that CM-LPS could be internalized and ultimately attenuate the deleterious effects of pro-inflammatory molecules like tumor necrosis factor-α (TNF-α) and platelet activating factor (PAF) on endothelial permeability. Here, we show that CM-LPS complexes induce cytokine tolerance in endothelial cells. In rats, TNF-α increased hydraulic conductivity 2.5-fold over baseline and PAF increased it 5-fold; but, pretreatment with CM-LPS or an attenuated analog (CM-LPS*) inhibited these changes. Nuclear/cytoplasmic levels of p65 were reduced afte...

【 授权许可】

CC BY