What question did this study set out to answer?

To elucidate how circulating plasma proteins and cell-intrinsic adaptation mechanisms regulate monocyte and macrophage responsiveness to lipopolysaccharide during Gram-negative endotoxemia.

October 7, 2008Pathobiology

Regulatory Mechanisms of Host Responsiveness to Endotoxin (Lipopolysaccharide)

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Authors

JMJohn C. MathisonScripps Research Institute PTPeter S. TobiasLinköping University EWEliza B. WolfsonRoslin Institute

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Implication

Laboratory study reveals how plasma proteins and cellular adaptation control macrophage responsiveness to endotoxin, highlighting pathways that balance immune defense and tissue injury.

Key Points

To elucidate how circulating plasma proteins and cell-intrinsic adaptation mechanisms regulate monocyte and macrophage responsiveness to lipopolysaccharide during Gram-negative endotoxemia.
Assessed tumor necrosis factor-α (TNF-α) release and mRNA expression from monocytes and macrophages stimulated with lipopolysaccharide (LPS).
Blocked receptor signaling and depleted binding factors using monoclonal antibodies against CD14 and LPS-binding protein (LBP) in whole blood and plasma.
Modeled cellular adaptation by pretreating macrophages with subthreshold concentrations (<100 pg/ml) of LPS for 6–9 hours prior to secondary challenge.
Depleting plasma LBP reduced cellular responsiveness to LPS at least 100-fold, anti-CD14 antibody reduced monocyte TNF-α release at least 10-fold, and LPS-lipoprotein complexes were up to 10,000-fold less active than LPS-LBP.
Low-dose LPS adaptation reduced macrophage sensitivity up to 1,000-fold, shifting the requirement for maximal TNF-α induction from 1 ng/ml to 1 µg/ml.
Adapted macrophages failed to exhibit the normal LPS-induced increase in steady-state TNF mRNA levels without showing increased mRNA degradation, a state reversible by exogenous LBP.

Cite This Study

Mathison et al. (2008) studied this question.

synapsesocial.com/papers/6aaa21bd0a88a9c60a4825d2 https://doi.org/10.1159/000163641

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Implication

Laboratory study reveals how plasma proteins and cellular adaptation control macrophage responsiveness to endotoxin, highlighting pathways that balance immune defense and tissue injury.

Regulatory Mechanisms of Host Responsiveness to Endotoxin (Lipopolysaccharide)

Discussion

Member takes

Implication

Key Points

Cite This Study

Regulatory Mechanisms of Host Responsiveness to Endotoxin (Lipopolysaccharide)

Discussion

Member takes

Implication

Key Points

Cite This Study

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