Advertisement

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

Barbara Thaler, Nagyung Baik, Philipp J. Hohensinner, Johanna Baumgartner, Adelheid Panzenböck, Stefan Stojkovic, Svitlana Demyanets, Ihor Huk, Gersina Rega-Kaun, Christoph Kaun, Manfred Prager, Michael B. Fischer, Kurt Huber, Walter S. Speidl, Robert J. Parmer, Lindsey A. Miles and Johann Wojta

Key Points

  • Plasminogen receptorKT facilitates migration of proinflammatory monocyte and macrophage subsets

Abstract

Membrane bound plasmin is used by immune cells to degrade extracellular matrices, which facilitates migration. The plasminogen receptor Plg-RKT is expressed by immune cells including monocytes and macrophages. Among monocytes and macrophages distinct subsets can be distinguished based on cell surface markers and pathophysiological function. We investigated expression of Plg-RKT by monocyte and macrophage subsets and whether potential differential expression might have functional consequences for cell migration. Pro-inflammatory CD14++CD16+ human monocytes and Ly6Chigh mouse monocytes expressed the highest levels of Plg-RKT and bound significantly more plasminogen compared to the other respective subsets. Pro-inflammatory human macrophages, generated by polarization with lipopolysaccharide and interferon-γ, showed significantly higher expression of Plg-RKT compared to alternatively activated macrophages, polarized with interleukin-4 and interleukin-13. Directional migration of pro-inflammatory monocytes was plasmin-dependent and was abolished by anti-Plg-RKT mAb, epsilon-amino-caproic acid, aprotinin and the aminoterminal fragment of urokinase-type plasminogen activator. In an in vivo peritonitis model significantly less Ly6Chigh monocyte recruitment was observed in Plg-RKT-/- compared with Plg-RKT+/+ mice. Immunohistochemical analysis of human carotid plaques and adipose tissue showed that pro-inflammatory macrophages also exhibited high levels of Plg-RKT in vivo. Our data demonstrate higher expression of Plg-RKT on pro-inflammatory monocyte and macrophage subsets that impacts their migratory capacity.

  • Submitted May 14, 2018.
  • Revision received June 20, 2019.
  • Accepted June 5, 2019.