Vimentin is secreted by activated macrophages

Area of Science:

• Immunology
• Cell Biology

Background:

• Vimentin, an intermediate filament protein, is primarily known for structural roles in processes like wound healing.
• The maturation of monocytes into macrophages involves complex signaling pathways.
• Phosphorylation of vimentin influences its intracellular localization and function.

Purpose of the Study:

• To investigate the secretion of vimentin by activated human macrophages.
• To elucidate the signaling pathways regulating vimentin secretion.
• To determine the role of extracellular vimentin in macrophage functions.

Main Methods:

• Utilized human monocyte-derived macrophages.
• Investigated vimentin secretion using phosphatase inhibitors (okadaic acid) and protein kinase C (PKC) inhibitors (GO6983).
• Examined the effects of cytokines (IL-10, TNF-alpha) on vimentin secretion.
• Assessed the role of extracellular vimentin in bacterial killing and oxidative metabolite generation.

Main Results:

• Activated human macrophages secrete vimentin into the extracellular space.
• Vimentin secretion is enhanced by okadaic acid and inhibited by GO6983, indicating PKC involvement.
• Interleukin-10 (IL-10) blocks vimentin secretion, while tumor necrosis factor alpha (TNF-alpha) triggers it.
• Extracellular vimentin contributes to bacterial killing and oxidative metabolite production by macrophages.

Conclusions:

• Vimentin is actively secreted by macrophages, particularly in response to pro-inflammatory signals.
• Macrophage-secreted vimentin plays a role in immune functions, including pathogen clearance.
• This finding expands the known functions of vimentin beyond structural support to include active participation in innate immunity.