Tumour necrosis factor-alpha interacts with laminin and functions as a pro-adhesive cytokine.
Certain cytokines, chemokines and growth factors interact with components of the extracellular matrix (ECM) and, in particular, sulphated polysaccharides and proteoglycans. Recently, we demonstrated that tumour necrosis factor-alpha (TNF-alpha), an inflammatory cytokine, can bind fibronectin (FN), a cell-adhesive glycoprotein of the ECM, and that TNF-alpha bound to FN enhances the binding of T cells to the glycoprotein. In the present study, we studied the interactions of TNF-alpha and laminin (LN), another glycoprotein present in basement membranes and extracellular matrices. 125I-labelled TNF-alpha was found to bind to immobilized LN, and more avidly to the E1 and P1 fragments of LN, which contain its integrin- and non-integrin-dependent cell-adhesive sites, suggesting that cryptic TNF-alpha-binding sites are exposed upon proteolytic fragmentation of LN by enzymes such as elastase or pepsin. The bound cytokine did not dissociate from the LN and its fragments during a 24-hr period, indicating that in vivo LN can serve to restrict TNF-alpha adjacent to inflammatory sites. The LN-associated TNF-alpha retained at least some of its biological activities, since both diffusible and, to a greater extent, LN-bound TNF-alpha elevated the beta 1-integrin-dependent adhesion to LN of phorbol ester-activated human CD4+ T cells. Thus, LN and TNF-alpha may act in concert to transmit synergistic activating signals to infiltrating leucocytes, and thereby regulate immune cell reactions in extravascular inflammatory tissue.
Hershkoviz
R
R
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Goldkorn
I
I
Lider
O
O
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007797:Laminin / Q000378:metabolism*; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D007797:Laminin; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha