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

Y Tanaka, D H Adams, S Hubscher, H Hirano, U Siebenlist, S Shaw

Research output: Contribution to journalArticlepeer-review

833 Citations (Scopus)


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


  • 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


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