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Soluble CD14 participates in the response of cells to lipopolysaccharide
E A Frey1, D S Miller, T G Jahr
1Department of Biochemistry, University of British Columbia, Vancouver, Canada.
Abstract:
CD14 is a 55-kD protein found both as a glycosylphosphatidyl inositol-linked protein on the surface of mononuclear phagocytes and as a soluble protein in the blood. CD14 on the cell membrane (mCD14) has been shown to serve as a receptor for complexes of lipopolysaccharide (LPS) with LPS binding protein, but a function for soluble CD14 (sCD14) has not been described. Here we show that sCD14 enables responses to LPS by cells that do not express CD14. We have examined induction of endothelial-leukocyte adhesion molecule 1 expression by human umbilical vein endothelial cells, interleukin 6 secretion by U373 astrocytoma cells, and cytotoxicity of bovine endothelial cells. None of these cell types express mCD14, yet all respond to LPS in a serum-dependent fashion, and all responses are completely blocked by anti-CD14 antibodies. Immunodepletion of sCD14 from serum prevents responses to LPS, and the responses are restored by addition of sCD14. These studies suggest that a surface anchor is not needed for the function of CD14 and further imply that sCD14 must bind to additional proteins on the cell surface to associate with the cell and transduce a signal. They also indicate that sCD14 may have an important role in potentiating responses to LPS in cells lacking mCD14.
Insights
Soluble CD14 (sCD14) enables cells lacking membrane CD14 (mCD14) to respond to lipopolysaccharide (LPS). This suggests sCD14 can function independently of a cell surface anchor, highlighting its role in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD14 is a protein present on mononuclear phagocytes and in blood.
- Membrane-bound CD14 (mCD14) acts as a lipopolysaccharide (LPS) receptor.
- The function of soluble CD14 (sCD14) was previously unknown.
Purpose of the Study:
- To investigate the function of soluble CD14 (sCD14).
- To determine if sCD14 can mediate cellular responses to LPS in cells lacking mCD14.
Main Methods:
- Examined induction of endothelial-leukocyte adhesion molecule 1 expression in endothelial cells.
- Assessed interleukin 6 secretion by astrocytoma cells.
- Evaluated cytotoxicity of endothelial cells in response to LPS.
- Utilized serum immunodepletion and sCD14 addition experiments.
Main Results:
- Cells lacking mCD14 responded to LPS in a serum-dependent manner.
- These responses were blocked by anti-CD14 antibodies.
- Depleting sCD14 from serum abolished LPS responses, which were restored by adding sCD14.
Conclusions:
- Soluble CD14 (sCD14) enables LPS responses in cells without membrane CD14 (mCD14).
- sCD14 does not require a surface anchor to function, suggesting interaction with other cell surface proteins.
- sCD14 plays a significant role in potentiating LPS responses in cells lacking mCD14.