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Evidence that the receptor for soluble CD14:LPS complexes may not be the putative signal-transducing molecule
1Division of Molecular Medicine, North Shore University Hospital, Cornell University Medical College, Manhasset, NY 11030, USA.
Abstract:
Membrane-bound CD14 acts as a receptor for lipopolysaccharide (LPS) on monocytes/macrophages and neutrophils. Studies have suggested that the activation of monocytes/macrophages by the binding of LPS to membrane-bound CD14 may require the association of a signal-transducing molecule with membrane-bound CD14. The observation that non-CD14 expressing cells, such as endothelial cells, can nevertheless be activated by a complex of LPS and a soluble form of CD14 (sCD14) suggests that the receptor for this complex may be identical to the signal transducing molecule associated with membrane-bound CD14. The studies described show that two CD14-specific MoAb are able to block the LPS-induced activation of endothelial cells but do not affect the response of monocytes to LPS. This suggests that the interaction of the sCD14:LPS complex with endothelial cells is distinct from the interaction of membrane-bound CD14 with its putative signal-transducing molecule.
Insights
Soluble CD14 (sCD14) and lipopolysaccharide (LPS) activate endothelial cells via a distinct pathway from membrane-bound CD14 activation on monocytes. This suggests a novel receptor interaction for the sCD14:LPS complex.
Area of Science:
- Immunology
- Cell Biology
Background:
- Membrane-bound CD14 functions as a lipopolysaccharide (LPS) receptor on immune cells like monocytes and macrophages.
- LPS binding to membrane-bound CD14 may necessitate association with a signal-transducing molecule for monocyte activation.
- Endothelial cells, lacking membrane-bound CD14, can be activated by a soluble CD14 (sCD14):LPS complex, implying a different receptor mechanism.
Purpose of the Study:
- To investigate the distinct mechanisms of LPS-induced cell activation mediated by membrane-bound CD14 versus the sCD14:LPS complex.
- To differentiate the receptor interactions involved in monocyte and endothelial cell responses to LPS.
Main Methods:
- Utilized CD14-specific monoclonal antibodies (MoAb) to block LPS-induced cell activation.
- Compared the effects of MoAb on LPS activation in monocytes versus endothelial cells.
- Analyzed the distinct signaling pathways triggered by membrane-bound CD14 and the sCD14:LPS complex.
Main Results:
- Two CD14-specific MoAb successfully blocked LPS-induced activation of endothelial cells.
- These same MoAb did not inhibit the LPS response in monocytes.
- Demonstrated that the endothelial cell response to the sCD14:LPS complex is mediated by a pathway separate from membrane-bound CD14 signaling.
Conclusions:
- The interaction of the sCD14:LPS complex with endothelial cells involves a receptor distinct from membrane-bound CD14.
- Endothelial cell activation by sCD14:LPS suggests a novel signaling pathway independent of classical CD14-mediated monocyte activation.
- Further research is warranted to identify the specific receptor mediating endothelial cell response to the sCD14:LPS complex.