T-cell Adhesion Induced by Proteoglycan-Immobilized Cytokine MIP-1 Beta

Nature. 1993 Jan 7;361(6407):79-82. doi: 10.1038/361079a0.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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