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CD14 is a cell-activating receptor for bacterial peptidoglycan
D Gupta1, T N Kirkland, S Viriyakosol
1Northwest Center for Medical Education, Indiana University School of Medicine, Gary, Indiana 46408, USA.
The Journal of Biological Chemistry
|September 20, 1996
Summary
CD14 acts as a cell-activating receptor for bacterial peptidoglycan, not just endotoxin. This discovery reveals CD14
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- CD14 is known as an endotoxin receptor on macrophages and neutrophils.
- The role of CD14 in recognizing bacterial peptidoglycan was previously unclear.
Purpose of the Study:
- To investigate if CD14 functions as a cell-activating receptor for bacterial peptidoglycan.
- To elucidate the specific regions of CD14 involved in peptidoglycan and endotoxin recognition.
Main Methods:
- Transfection of mouse 70Z/3 cells with human CD14.
- Stimulation with insoluble and soluble peptidoglycan and endotoxin.
- Analysis of surface IgM expression, NF-kappaB activation, and IkappaB-alpha degradation.
- Utilizing CD14 deletion mutants and anti-CD14 monoclonal antibodies.
Main Results:
- 70Z/3-CD14 cells responded to peptidoglycan and endotoxin, unlike control cells.
- Peptidoglycan-induced responses were not inhibited by polymyxin B, distinguishing them from endotoxin effects.
- Both peptidoglycan and endotoxin responses were blocked by anti-CD14 antibodies.
- Specific N-terminal regions of CD14 were critical for differential responses to peptidoglycan and endotoxin.
Conclusions:
- CD14 is identified as the functional receptor for bacterial peptidoglycan.
- Similar, yet distinct, N-terminal sequences in CD14 mediate responses to both peptidoglycan and endotoxin.
- This finding expands the known functions of CD14 in innate immunity.