Document Detail


Classically activated macrophages use stable microtubules for matrix metalloproteinase-9 (MMP-9) secretion.
MedLine Citation:
PMID:  22270361     Owner:  NLM     Status:  Publisher    
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 upregulate 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 PDI, 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     Date:  2012-1-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
University of Ottawa, Canada;
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