T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta

Research output: Contribution to journalArticlepeer-review

Authors

  • Y Tanaka
  • H Hirano
  • U Siebenlist
  • S Shaw

Abstract

Lymphocyte migration from blood into tissue depends on integrin-mediated adhesion to endothelium. Adhesion requires not only integrin ligands on the endothelium, but also activation signals because T-cell integrins cannot bind well until they are activated. The physiological 'triggers' for T-cell adhesion are unknown, but cytokines may be good candidates as they are released during inflammation and trigger adhesion in neutrophils and monocytes. We have identified a cytokine, macrophage inflammatory protein-1 beta (MIP-1 beta), that induces both chemotaxis and adhesion of T cells; MIP-1 beta is most effective at augmenting adhesion of CD8+ T cells to the vascular cell adhesion molecule VCAM-1. We reasoned that, as cytokines in vivo will be rapidly washed away, MIP-1 beta might be bound to endothelial surfaces and so induce adhesion in its immobilized form. Here we show that: (1) MIP-1 beta is present on lymph node endothelium; (2) immobilized MIP-1 beta induces binding of T cells to VCAM-1 in vitro. MIP-1 beta was immobilized by binding to proteoglycan: a conjugate of heparin with bovine serum albumin and cellular proteoglycan CD44 were both effective. We propose that MIP-1 beta and other cytokines with glycosaminoglycan-binding sites will bind to and be presented by endothelial proteoglycans to trigger adhesion selectively not only of lymphocyte subsets, but also of other cell types.

Details

Original languageEnglish
Pages (from-to)79-82
Number of pages4
JournalNature
Volume361
Issue number6407
Publication statusPublished - 7 Jan 1993

Keywords

  • Cell Adhesion, Cell Adhesion Molecules, Chemokine CCL4, Chemotaxis, Cytokines, Heparin, Humans, Macrophage Inflammatory Proteins, Monokines, Proteoglycans, Receptors, Lymphocyte Homing, Serum Albumin, Bovine, T-Lymphocytes, Vascular Cell Adhesion Molecule-1