Lymphocytes perform reverse adhesive haptotaxis mediated by LFA-1 integrins

J Cell Sci. 2020 Aug 25;133(16):jcs242883. doi: 10.1242/jcs.242883.

Abstract

Cell guidance by anchored molecules, or haptotaxis, is crucial in development, immunology and cancer. Adhesive haptotaxis, or guidance by adhesion molecules, is well established for mesenchymal cells such as fibroblasts, whereas its existence remains unreported for amoeboid cells that require less or no adhesion in order to migrate. We show that, in vitro, amoeboid human T lymphocytes develop adhesive haptotaxis mediated by densities of integrin ligands expressed by high endothelial venules. Moreover, lymphocytes orient towards increasing adhesion with VLA-4 integrins (also known as integrin α4β1), like all mesenchymal cells, but towards decreasing adhesion with LFA-1 integrins (also known as integrin αLβ4), which has not previously been observed. This counterintuitive 'reverse haptotaxis' cannot be explained by existing mechanisms of mesenchymal haptotaxis involving either competitive anchoring of cell edges under tension or differential integrin-activated growth of lamellipodia, because they both favor orientation towards increasing adhesion. The mechanisms and functions of amoeboid adhesive haptotaxis remain unclear; however, multidirectional integrin-mediated haptotaxis might operate around transmigration ports on endothelia, stromal cells in lymph nodes, and inflamed tissue where integrin ligands are spatially modulated.

Keywords: Amoeboid migration; Cell guidance; Haptotaxis; Integrins; LFA-1; Lymphocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adhesives
  • Cell Adhesion
  • Chemotaxis
  • Humans
  • Integrins*
  • Lymphocyte Function-Associated Antigen-1*
  • Lymphocytes
  • Vascular Cell Adhesion Molecule-1

Substances

  • Adhesives
  • Integrins
  • Lymphocyte Function-Associated Antigen-1
  • Vascular Cell Adhesion Molecule-1