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.
Original language | English |
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Pages (from-to) | 79-82 |
Number of pages | 4 |
Journal | Nature |
Volume | 361 |
Issue number | 6407 |
DOIs | |
Publication status | Published - 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