Cross-linking of protein S bound to lymphocytes promotes aggregation and inhibits proliferation.
Recently, we reported that expression of the anticoagulant protein S is IL-4-inducible in primary T cells, and that protein S inhibits lymphoid cell procoagulant activity. Here, using a flow cytometric assay, we demonstrate that protein S binds to the surface of B and T lymphocytes. In addition, we show that cross-linking of protein S bound to lymphocytes induces aggregation and inhibits growth in cultures of primary B and T lymphocytes. Thus, our studies suggest that protein S is an IL-4-inducible T cell product that can affect B and T cell growth and aggregation via a lymphocyte protein S receptor. Interestingly, protein S joins thrombin and factor Xa as coagulation factors that modulate lymphocyte activation, suggesting that the clotting pathway may regulate wound-related inflammatory responses.
Smiley
S T
ST
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Stitt
T N
TN
Grusby
M J
MJ
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D006131:Growth Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016853:Muromonab-CD3 / Q000494:pharmacology; D011485:Protein Binding; D017293:Protein S / Q000378:metabolism / Q000494:pharmacology*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction
D000888:Antibodies, Anti-Idiotypic; D006131:Growth Inhibitors; D008070:Lipopolysaccharides; D016853:Muromonab-CD3; D017293:Protein S; D011956:Receptors, Cell Surface; C044203:anti-IgM; C109529:protein S receptor, mouse; D003208:Concanavalin A; D020794:Receptor Protein-Tyrosine Kinases; C084944:TYRO3 protein, human