Document Detail


Chemerin activation by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades.
MedLine Citation:
PMID:  16096270     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proteases function at every level in host defense, from regulating vascular hemostasis and inflammation to mobilizing the "rapid responder" leukocytes of the immune system by regulating the activities of various chemoattractants. Recent studies implicate proteolysis in the activation of a ubiquitous plasma chemoattractant, chemerin, a ligand for the G-protein-coupled receptor CMKLR1 present on plasmacytoid dendritic cells and macrophages. To define the pathophysiologic triggers of chemerin activity, we evaluated the ability of serum- and inflammation-associated proteases to cleave chemerin and stimulate CMKLR1-mediated chemotaxis. We showed that serine proteases factor XIIa and plasmin of the coagulation and fibrinolytic cascades, elastase and cathepsin G released from activated neutrophil granules and mast cell tryptase are all potent activators of chemerin. Activation results from cleavage of the labile carboxyl terminus of the chemoattractant at any of several different sites. Activation of chemerin by the serine protease cascades that trigger rapid defenses in the body may direct CMKLR1-positive plasmacytoid dendritic cell and tissue macrophage recruitment to sterile sites of tissue damage, as well as trafficking to sites of infectious and allergic inflammation.
Authors:
Brian A Zabel; Samantha J Allen; Paulina Kulig; Jessica A Allen; Joanna Cichy; Tracy M Handel; Eugene C Butcher
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2005-08-11
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Oct 
Date Detail:
Created Date:  2005-10-10     Completed Date:  2005-12-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34661-6     Citation Subset:  IM    
Affiliation:
Laboratory of Immunology and Vascular Biology, Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA. bazabel@alum.mit.edu
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Baculoviridae / genetics
Binding Sites
Cathepsin G
Cathepsins / chemistry,  pharmacology
Chemokines / chemistry*
Chemotaxis
Culture Media, Conditioned / pharmacology
Culture Media, Serum-Free / pharmacology
Dendritic Cells / cytology
Escherichia coli / metabolism
Factor XIIa / chemistry
Fibrinolysin / chemistry,  metabolism
Humans
Inflammation
Ligands
Macrophages / cytology,  metabolism
Mass Spectrometry
Mast Cells / cytology
Models, Biological
Molecular Sequence Data
Neutrophils / metabolism
Pancreatic Elastase / chemistry,  metabolism
Plasmacytoma / metabolism
Protein Structure, Tertiary
Recombinant Fusion Proteins / chemistry
Serine Endopeptidases / chemistry*,  pharmacology
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Time Factors
Transfection
Trypsin / chemistry
Tryptases
Grant Support
ID/Acronym/Agency:
AI-37832/AI/NIAID NIH HHS; AI-47822/AI/NIAID NIH HHS; AI-59635/AI/NIAID NIH HHS; AI37113-09/AI/NIAID NIH HHS; DK56339/DK/NIDDK NIH HHS; GM-37734/GM/NIGMS NIH HHS; HL-67674/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Culture Media, Conditioned; 0/Culture Media, Serum-Free; 0/Ligands; 0/Recombinant Fusion Proteins; 0/chemerin, human; EC 3.4.-/Cathepsins; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.20/CTSG protein, human; EC 3.4.21.20/Cathepsin G; EC 3.4.21.36/Pancreatic Elastase; EC 3.4.21.38/Factor XIIa; EC 3.4.21.4/Trypsin; EC 3.4.21.59/Tryptases; EC 3.4.21.7/Fibrinolysin

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