Regulation of adhesion of CD4+ T lymphocytes to intact or heparinase-treated subendothelial extracellular matrix by diffusible or anchored RANTES and MIP-1 beta.
Chemokines, a superfamily of 8- to 11-kDa mediators of inflammation, affect the attachment of immune cells to vascular endothelia by binding to cell surface glycosaminoglycans. We analyzed whether chemokines are also involved in interactions between CD4+ T lymphocytes and the subendothelial extracellular matrix (ECM). Soluble mediators, such as MIP-1 beta and RANTES, induced the binding of resting human CD4+ T cells to ECM in an integrin-dependent manner. Both MIP-1 beta and RANTES bound to intact ECM and retained their adhesive properties, and moreover, ECM-bound RANTES and MIP-1 beta prolonged the time course of interactions between the CD4+ T cells and the ECM. Because the adhesive effect of these chemokines was restricted by an inhibitor of GTP-binding proteins, the adhesive effect of ECM-bound RANTES and MIP-1 beta, which requires an intact cytoskeleton, seems to involve activation of a G protein-linked receptor. MIP-1 beta and RANTES exert their pro-adhesive effects through interactions with glycosaminoglycans, because heparinase-treated ECM did not bound chemokines and because the chemokines ability to induce T cell adhesion was abrogated if: 1) either of the chemokines is pretreaed with heparin or heparan-sulfate (HS), 2) HS is removed from intact ECM by heparinase, an HS-specific endoglycosidase, or 3) the ECM-bound chemokines are released by pretreatment with heparinase. Hence, the adhesive effects of immobilized chemokines is not restricted to T cells interacting with endothelial cells, but also affects the migration of immune cells which reside and function in the context of ECM.
Gilat
D
D
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Mekori
Y A
YA
Vlodavsky
I
I
Lider
O
O
D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology*; D002478:Cells, Cultured; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology*; D019763:Heparin Lyase; D006801:Humans; D008222:Lymphokines / Q000378:metabolism / Q000502:physiology*; D019402:Macrophage Inflammatory Proteins; D015846:Monokines / Q000378:metabolism / Q000502:physiology*; D011133:Polysaccharide-Lyases / Q000502:physiology; D011485:Protein Binding / Q000276:immunology
D054407:Chemokine CCL4; D018946:Chemokine CCL5; D016207:Cytokines; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase