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Plasminogen-mediated matrix invasion and degradation by macrophages is dependent on surface expression of annexin II

D J Falcone1, W Borth, K M Khan

  • 1Departments of Pathology, Cell Biology, Pediatrics, and Medicine, Joan and Sanford I. Weill Medical College of Cornell University, New York, NY, USA. dfalcone@mail.med.cornell.edu

Blood
|February 7, 2001
PubMed

Insights

Annexin II on macrophages binds plasminogen, crucial for cell migration and debris clearance. This protein facilitates macrophage invasion and degradation of extracellular matrices during inflammation.

Area of Science:

  • Cell Biology
  • Immunology
  • Biochemistry

Background:

  • Plasminogen activation is vital for macrophage functions, including migration, debris removal, and fibrin clearance at injury sites.
  • Macrophage surface proteins play a key role in their interaction with extracellular matrices and inflammatory responses.

Purpose of the Study:

  • To identify and characterize the plasminogen binding protein on macrophages.
  • To elucidate the role of annexin II in macrophage migration, extracellular matrix degradation, and plasminogen activation.

Main Methods:

  • Flow cytometry and Western blot analysis to detect calcium-dependent annexin II binding to macrophages.
  • Ligand blotting to identify proteins that bind plasminogen.
  • Inhibition assays using anti-annexin II IgG to assess the impact on plasminogen and plasmin binding.
  • Assays measuring plasminogen activation, extracellular matrix degradation, and monocyte chemotaxis.

Main Results:

  • Annexin II was identified as a plasminogen binding protein on the surface of RAW264.7 macrophages.
  • Anti-annexin II antibodies inhibited plasminogen and plasmin binding to macrophages.
  • Inhibition of annexin II-plasminogen binding impaired macrophage plasminogen activation and extracellular matrix degradation.
  • Annexin II blockade reduced plasminogen-dependent monocyte migration through extracellular matrices.

Conclusions:

  • Annexin II serves as a critical plasminogen binding site on macrophages.
  • Annexin II is essential for the invasive and degradative functions of macrophages.
  • Targeting annexin II may modulate macrophage-mediated inflammatory processes.

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