T-cell adhesion induced by proteoglycan-immobilized cytokine MIP-1 beta.
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.
Tanaka
Y
Y
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Adams
D H
DH
Hubscher
S
S
Hirano
H
H
Siebenlist
U
U
Shaw
S
S
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D054407:Chemokine CCL4; D002633:Chemotaxis; D016207:Cytokines / Q000502:physiology*; D006493:Heparin; D006801:Humans; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D012710:Serum Albumin, Bovine; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011509:Proteoglycans; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D012710:Serum Albumin, Bovine; D006493:Heparin