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Moesin: a potential LPS receptor on human monocytes
1Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, Boston, Massachusetts 02118, USA. samar@bu.edu
Journal of Endotoxin Research
|November 22, 2001
Summary
Bacterial lipopolysaccharide (LPS) triggers inflammation via CD14, but a second receptor, Moesin, also binds LPS. Blocking Moesin significantly reduces LPS-induced TNF-alpha, suggesting its role in inflammatory responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Bacterial endotoxin (lipopolysaccharide, LPS) from Gram-negative bacteria induces pro-inflammatory cytokines, contributing to conditions like septic shock and periodontal disease.
- CD14 is a known LPS receptor on monocytes/macrophages, but its lack of a cytoplasmic domain suggests involvement of other signaling molecules.
- Toll proteins have been implicated in LPS-mediated signaling pathways.
Purpose of the Study:
- To identify and characterize secondary LPS-binding cell surface domains on monocytes/macrophages.
- To investigate the role of these secondary domains in LPS-induced inflammatory responses.
Main Methods:
- Experiments utilizing anti-CD14 blocking antibodies to assess partial inhibition of LPS-induced TNF-alpha.
- Cross-linking assays to identify LPS binding sites, followed by mass spectroscopic analysis for protein identification.
- Utilizing anti-Moesin monoclonal antibodies to block LPS-mediated responses and assess specificity.
- Evaluating the effect of anti-Moesin on monocyte chemotaxis and cytokine production.
- Histological analysis of LPS-induced skin lesions in Moesin-deficient and wild-type mice.
Main Results:
- Anti-CD14 antibody only partially blocked LPS-induced TNF-alpha, indicating a second receptor.
- Cross-linking identified a 78 kDa domain, identified as Moesin, in addition to the 55 kDa CD14 receptor.
- Anti-Moesin antibody dose-dependently blocked LPS-induced TNF-alpha secretion.
- Anti-Moesin specifically blocked LPS-mediated events, not responses to other stimuli or basal monocyte functions.
- Moesin-deficient mice showed a significant reduction in neutrophil infiltration in LPS-induced skin lesions.
Conclusions:
- Moesin functions as an independent LPS receptor on human monocytes.
- Moesin plays a significant role in mediating LPS-induced inflammatory responses, particularly neutrophil recruitment.
- These findings reveal a novel mechanism in LPS signaling and suggest Moesin as a potential therapeutic target.