Plasminogen and plasmin can bind to human T cells and generate truncated CCL21 that increases dendritic cell chemotactic responses

J Biol Chem. 2022 Jul;298(7):102112. doi: 10.1016/j.jbc.2022.102112. Epub 2022 Jun 9.


Plasmin is a broad-spectrum protease and therefore needs to be tightly regulated. Active plasmin is formed from plasminogen, which is found in high concentrations in the blood and is converted by the plasminogen activators. In the circulation, high levels of α2-antiplasmin rapidly and efficiently inhibit plasmin activity. Certain myeloid immune cells have been shown to bind plasmin and plasminogen on their cell surface via proteins that bind to the plasmin(ogen) kringle domains. Our earlier work showed that T cells can activate plasmin but that they do not themselves express plasminogen. Here, we demonstrate that T cells express several known plasminogen receptors and that they bind plasminogen on their cell surface. We show T cell-bound plasminogen was converted to plasmin by plasminogen activators upon T cell activation. To examine functional consequences of plasmin generation by activated T cells, we investigated its effect on the chemokine, C-C motif chemokine ligand 21 (CCL21). Video microscopy and Western blotting confirmed that plasmin bound by human T cells cleaves CCL21 and increases the chemotactic response of monocyte-derived dendritic cells toward higher CCL21 concentrations along the concentration gradient by increasing their directional migration and track straightness. These results demonstrate how migrating T cells and potentially other activated immune cells may co-opt a powerful proteolytic system from the plasma toward immune processes in the peripheral tissues, where α2-antiplasmin is more likely to be absent. We propose that plasminogen bound to migrating immune cells may strongly modulate chemokine responses in peripheral tissues.

Keywords: T-cell; T-cell biology; cell migration; cell motility; chemokine; chemotaxis; microscopy; plasmin; plasminogen; plasminogen regulation.

MeSH terms

  • Antifibrinolytic Agents
  • Chemokine CCL21 / metabolism*
  • Chemokines
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Fibrinolysin / metabolism
  • Humans
  • Ligands
  • Plasminogen / metabolism*
  • Plasminogen Activators / metabolism
  • T-Lymphocytes / metabolism*
  • alpha-2-Antiplasmin


  • Antifibrinolytic Agents
  • CCL21 protein, human
  • Chemokine CCL21
  • Chemokines
  • Ligands
  • alpha-2-Antiplasmin
  • Plasminogen
  • Plasminogen Activators
  • Fibrinolysin