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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/33690

Title: Investigation of the Production, Distribution, and Trafficking of MMP-9 in Classically Activated Macrophages
Authors: Hanania, Raed
Advisor: Harrison, Rene E.
Department: Cell and Systems Biology
Keywords: macrophages
Macrophage activation
Matrix Metalloproteinase 9
Issue Date: 29-Nov-2012
Abstract: 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 stabilization and secretion of MMPs. Macrophages upregulate MMP-9 expression and secretion upon immunological challenge, and require its activity for migration during 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 contain calreticulin and PDI, in activated macrophages. Vesicular organelles of MMP-9 aligned along stable subsets of microtubules and colocalized with the anterograde molecular motor protein, kinesin. We demonstrated a functional contribution of stable MTs in the enhanced trafficking of MMP-9 extracellularly, and showed that heterogeneity exists in macrophage cell populations with respect to MMP-9 production.
URI: http://hdl.handle.net/1807/33690
Appears in Collections:Master

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