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Endotoxin-neutralizing capacity of soluble CD14
C Schütt1, T Schilling, U Grunwald
1Dept. Medical Immunology, Ernst-Moritz-Arndt-University Greifswald, Germany.
Research in Immunology
|January 1, 1992
Summary
Soluble CD14 (sCD14) reduces lipopolysaccharide (LPS)-induced monocyte activation and reactive oxygen species generation. Elevated sCD14 may protect against excessive monocyte mediator production, suggesting a therapeutic role in endotoxic shock.
Area of Science:
- Immunology
- Cell Biology
Background:
- Soluble CD14 (sCD14) plays a role in monocyte activation by lipopolysaccharide (LPS).
- LPS requires serum factors like LPS-binding proteins to activate monocytes.
- CD14-negative monocytes can still be activated by opsonized LPS via alternative receptors.
Purpose of the Study:
- To investigate the effect of sCD14 on endotoxin-inducible reactive oxygen species (ROS) generation in human monocytes.
- To explore the mechanism by which sCD14 influences LPS-monocyte interactions.
- To examine the release of sCD14 from monocytes stimulated by various cytokines and LPS.
Main Methods:
- Luminol-enhanced chemiluminescence was used to measure ROS production.
- Flow cytometry (FACS) with anti-mouse Ig-coated microbeads was employed to analyze antibody binding.
- Monocyte cultures were stimulated with LPS, TNF-alpha, IL-1, IL-4, IL-6, and IFN-gamma to measure sCD14 release.
Main Results:
- sCD14 dose-dependently reduced LPS-inducible monocyte activation, even in CD14-negative cells.
- sCD14 mediated the binding of an anti-CD14 antibody to LPS/LPS-binding protein complexes.
- LPS and TNF-alpha increased sCD14 release, while IL-4 decreased it; IL-1, IL-6, and IFN-gamma had no significant effect.
Conclusions:
- sCD14 inhibits LPS-induced monocyte activation and ROS production.
- Elevated sCD14 serum levels in polytraumatized patients might represent a protective mechanism against excessive inflammation.
- sCD14 holds potential as a therapeutic strategy for preventing endotoxic shock.