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Differential expression of Plg-RKT and its effects on migration of proinflammatory monocyte and macrophage subsets

Barbara Thaler1, Nagyung Baik2, Philipp J Hohensinner1

  • 1Department of Internal Medicine II, Medical University of Vienna, Vienna, Austria.

Blood
|June 22, 2019
PubMed

Insights

Proinflammatory monocytes and macrophages express higher levels of the plasminogen receptor Plg-RKT, enhancing their migration. This receptor is crucial for immune cell movement and recruitment in inflammatory conditions.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Immune cell migration is vital for tissue repair and inflammation.
  • Extracellular matrix degradation, facilitated by membrane-bound plasmin, is essential for cell movement.
  • The plasminogen receptor Plg-RKT is expressed on immune cells like monocytes and macrophages.

Purpose of the Study:

  • To investigate the expression of Plg-RKT in different monocyte and macrophage subsets.
  • To determine if differential Plg-RKT expression affects cell migration.
  • To explore the functional role of Plg-RKT in immune cell trafficking.

Main Methods:

  • Flow cytometry to analyze Plg-RKT expression on human and mouse monocyte subsets.
  • Macrophage polarization using LPS/IFN-γ and IL-4/IL-13 to generate proinflammatory and alternatively activated subsets.
  • In vitro migration assays using blocking antibodies and inhibitors.
  • In vivo peritonitis model in Plg-RKT knockout and wild-type mice.
  • Immunohistochemistry on human tissue samples (carotid plaques, adipose tissue).

Main Results:

  • Proinflammatory CD14++CD16+ human monocytes and Ly6Chigh mouse monocytes showed the highest Plg-RKT expression and plasminogen binding.
  • Proinflammatory macrophages exhibited significantly higher Plg-RKT expression than alternatively activated macrophages.
  • Monocyte migration was plasmin-dependent and inhibited by anti-Plg-RKT antibody and other inhibitors.
  • Reduced Ly6Chigh monocyte recruitment was observed in Plg-RKT knockout mice in vivo.
  • High Plg-RKT expression was confirmed on proinflammatory macrophages in human tissues.

Conclusions:

  • Plg-RKT is differentially expressed on monocyte and macrophage subsets, with higher levels on proinflammatory phenotypes.
  • Plg-RKT plays a critical role in regulating the migratory capacity of proinflammatory monocytes and macrophages.
  • Targeting Plg-RKT may offer a therapeutic strategy to modulate immune cell migration in inflammatory diseases.

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