Document Detail


Moesin functions as a lipopolysaccharide receptor on human monocytes.
MedLine Citation:
PMID:  10377093     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bacterial endotoxin (lipopolysaccharide [LPS]), a glycolipid found in the outer membranes of gram-negative bacteria, induces the secretion of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-6 by monocytes/macrophages. The secretion of these biologically active compounds leads to multiple pathological conditions, such as septic shock. There is substantial evidence that chronic exposure to LPS mediates, at least in part, the tissue destruction associated with gram-negative infection. CD14, a 55-kDa protein, has been identified as an LPS receptor. In conjunction with a serum protein, LPS binding protein (LBP), LPS-CD14 interactions mediate many LPS functions in the inflammatory response. However, CD14 lacks a cytoplasmic domain, or any known signal transduction sequence motif, suggesting the existence of another cell surface domain capable of transducing signals. In this paper, we report a second, CD14-independent LPS binding site, which, based on biological activity, appears to be a functional LPS receptor. Cross-linking experiments were performed to identify LPS binding sites. Two molecules were identified: a 55-kDa protein (CD14) and a second, 78-kDa band. Sequencing of the 78-kDa protein by mass spectroscopic analysis revealed 100% homology with moesin (membrane-organizing extension spike protein). Antibody to CD14 induced partial blocking of the LPS response. However, antimoesin monoclonal antibody completely blocked the LPS-induced TNF-alpha response in human monocytes, without blocking CD14 binding of LPS. Irrelevant isotype controls had no effect. Additional experiments were performed to evaluate the specificity of the antimoesin blocking. Separate experiments evaluated antimoesin effects on monocyte chemotaxis, IL-1 production in response to IL-1 stimulation, and TNF-alpha secretion in response to Staphylococcus aureus stimulation. Antimoesin blocked only LPS-mediated events. The data suggest that moesin functions as an independent LPS receptor on human monocytes. The role of moesin in transduction of CD14-mediated signals is discussed.
Authors:
Z N Tohme; S Amar; T E Van Dyke
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Infection and immunity     Volume:  67     ISSN:  0019-9567     ISO Abbreviation:  Infect. Immun.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-22     Completed Date:  1999-07-22     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3215-20     Citation Subset:  IM    
Affiliation:
Goldman School of Dental Medicine, Boston University, Boston, Massachusetts 02118, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Antigens, CD14 / genetics,  metabolism*
Cells, Cultured
Cytokines / metabolism
Humans
Lipopolysaccharides / metabolism*
Microfilament Proteins / genetics,  metabolism*
Molecular Sequence Data
Monocytes / metabolism*,  microbiology
Sequence Homology, Amino Acid
Grant Support
ID/Acronym/Agency:
DE06436/DE/NIDCR NIH HHS; DE07206/DE/NIDCR NIH HHS; DE10709/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD14; 0/Cytokines; 0/Lipopolysaccharides; 0/Microfilament Proteins; 144131-77-1/moesin
Comments/Corrections

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