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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
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Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages

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Matrix metalloproteinase inhibitors prevent the release and proteolytic activity of monocyte/macrophage-derived

Stefano Fogli1, Tommaso Neri2, Elisa Nuti3

  • 1Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Pharmacological Reports : PR
|April 21, 2019
PubMed
Abstract

Insights

Matrix metalloproteinase (MMP) inhibitors significantly reduce microparticle (MP) release from monocytes/macrophages. These MMP inhibitors also decrease the proteolytic activity of released MPs, offering potential therapeutic strategies for cancer and inflammation.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Monocyte/macrophage-derived microparticles (MPs) are implicated in cancer and chronic inflammation.
  • The precise mechanisms governing MP release remain largely unknown.

Purpose of the Study:

  • To investigate the potential of matrix metalloproteinase (MMP) inhibitors in preventing microparticle shedding from stimulated human monocytes/macrophages.

Main Methods:

  • Microparticles were generated from peripheral blood mononuclear cells stimulated with A23187.
  • MP shedding, intracellular calcium, RhoA expression, and MP proteolytic activity were measured with and without MMP inhibitors.

Main Results:

  • MMP inhibitors demonstrated a concentration-dependent reduction in MP shedding (IC50 in nano- to micromolar range).
  • Inhibitors decreased intracellular calcium levels and RhoA translocation, crucial for MP release.
  • MMP inhibitors effectively suppressed the proteolytic activity of released MPs.

Conclusions:

  • MMP inhibitors successfully prevent microparticle shedding and reduce the proteolytic activity of released MPs.
  • The most potent MMP inhibitor tested may serve as a lead compound for novel therapeutics targeting cancer and inflammatory diseases.
Keywords:
Matrix metalloproteinasesMicroparticlesMononuclear cells

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