Document Detail


Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers.
MedLine Citation:
PMID:  20083497     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heparin-binding protein (HBP), an evolutionary ancient and biologically highly important molecule in inflammation, is an inactive serine protease due to mutations in the catalytic triad. The histidine (position 41) in the conserved sequence TAAHC is mutated to serine and this sequence (TAASC) plays a crucial role when HBP binds to monocytes. We synthesized a 20-44 HBP peptide, cyclicized by a sulphur bridge, which encompasses this amino acid and functions as full-length HBP. Using a human monocyte cell line, we have shown that lipopolysaccharide (LPS)-triggered secretion of IL-6 is enhanced up to 10-fold when full-length HBP or the peptide are present in low-to-moderate concentrations. A monoclonal antibody neutralizing HBP also neutralizes the peptide, indicating that the ligand for the HBP receptor is located near serine in position 41 on the HBP surface. A 'back mutated' 20-44 peptide (serine→histidine) has some, but not significant, stimulatory effect on monocytes. Normally, HBP production and release is ascribed to neutrophil granulocytes, but here we find that also monocytes secrete HBP when stimulated with LPS. Furthermore, a small amount of HBP can be demonstrated when monocytes are incubated in medium alone. Our efforts to identify a suggested HBP receptor on monocytes has failed so far.
Authors:
Morten Schou; René Djurup; Kjeld Norris; Hans Flodgaard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-01-18
Journal Detail:
Title:  Innate immunity     Volume:  17     ISSN:  1753-4267     ISO Abbreviation:  Innate Immun     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-08     Completed Date:  2011-06-23     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  101469670     Medline TA:  Innate Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  60-9     Citation Subset:  IM    
Affiliation:
Bartholin Instituttet XPU, Biocenter Copenhagen, Rigshospitalet, Blegdamsvej 9, Copenhagen Ø, Denmark. morten.schou@rh.regionh.dk
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / immunology,  pharmacology
Antigens, CD18 / immunology
Antimicrobial Cationic Peptides / immunology,  metabolism*,  pharmacology*,  secretion
Blood / drug effects,  metabolism
Blood Proteins / immunology,  metabolism*,  pharmacology*,  secretion
Carrier Proteins / immunology,  metabolism*,  pharmacology*,  secretion
Cell Line
Culture Media / pharmacology
Humans
Interleukin-6 / metabolism
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Lipopolysaccharides / pharmacology
Monocytes / drug effects*,  metabolism*,  secretion
Peptide Fragments / pharmacology*
Peptidoglycan / pharmacology
Protein Interaction Domains and Motifs / physiology
Protein-Tyrosine Kinases / antagonists & inhibitors
Stilbenes / pharmacology
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD18; 0/Antimicrobial Cationic Peptides; 0/Blood Proteins; 0/Carrier Proteins; 0/Culture Media; 0/IL6 protein, human; 0/Interleukin-6; 0/Intracellular Signaling Peptides and Proteins; 0/Lipopolysaccharides; 0/Peptide Fragments; 0/Peptidoglycan; 0/Stilbenes; 0/cationic antimicrobial protein CAP 37, human; 4339-71-3/3,3',4,5'-tetrahydroxystilbene; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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