Document Detail


Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion.
MedLine Citation:
PMID:  22270361     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
As major effector cells of the innate immune response, macrophages must adeptly migrate from blood to infected tissues. Endothelial transmigration is accomplished by matrix metalloproteinase (MMP)-induced degradation of basement membrane and extracellular matrix components. The classical activation of macrophages with LPS and IFN-γ causes enhanced microtubule (MT) stabilization and secretion of MMPs. Macrophages up-regulate MMP-9 expression and secretion upon immunological challenge and require its activity for migration during the inflammatory response. However, the dynamics of MMP-9 production and intracellular distribution as well as the mechanisms responsible for its trafficking are unknown. Using immunofluorescent imaging, we localized intracellular MMP-9 to small Golgi-derived cytoplasmic vesicles that contained calreticulin and protein-disulfide isomerase in activated RAW 264.7 macrophages. We demonstrated vesicular organelles of MMP-9 aligned along stable subsets of MTs and showed that selective modulation of MT dynamics contributes to the enhanced trafficking of MMP-9 extracellularly. We found a Rab3D-dependent association of MMP-9 vesicles with the molecular motor kinesin, whose association with the MT network was greatly enhanced after macrophage activation. Finally, we implicated kinesin 5B and 3B isoforms in the effective trafficking of MMP-9 extracellularly.
Authors:
Raed Hanania; He Song Sun; Kewei Xu; Sofia Pustylnik; Sujeeve Jeganathan; Rene E Harrison
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-01-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  287     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-12     Completed Date:  2012-05-01     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8468-83     Citation Subset:  IM    
Affiliation:
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calreticulin / metabolism
Cell Line
Gene Expression Regulation, Enzymologic / drug effects,  physiology
Golgi Apparatus / enzymology
Kinesin / metabolism
Lipopolysaccharides / pharmacology,  physiology
Macrophage Activation / drug effects,  physiology*
Macrophages / cytology,  metabolism*
Matrix Metalloproteinase 9 / biosynthesis,  secretion*
Microtubules / metabolism*
Protein Disulfide-Isomerases / metabolism
Protein Transport / drug effects,  physiology
Secretory Vesicles / enzymology*
Up-Regulation / drug effects
rab3 GTP-Binding Proteins / metabolism
Grant Support
ID/Acronym/Agency:
MOP-68992//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Calreticulin; 0/Lipopolysaccharides; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.6.1.-/Kinesin; EC 3.6.1.-/Rab3d protein, mouse; EC 3.6.5.2/rab3 GTP-Binding Proteins; EC 5.3.4.1/Protein Disulfide-Isomerases
Comments/Corrections

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


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