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Vimentin is secreted by activated macrophages

Nirit Mor-Vaknin1, Antonello Punturieri, Kajal Sitwala

  • 1Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical Center, Ann Arbor, MI 48109-0640, USA.

Nature Cell Biology
|December 17, 2002
PubMed

Insights

Activated macrophages secrete vimentin, an intermediate filament protein, into extracellular spaces. This secretion, influenced by protein kinase C (PKC) signaling and cytokines like IL-10 and TNF-alpha, aids in bacterial killing and immune responses.

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.

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