Protein S is inducible by interleukin 4 in T cells and inhibits lymphoid cell procoagulant activity.
Extravascular procoagulant activity often accompanies cell-mediated immune responses and systemic administration of pharmacologic anticoagulants prevents cell-mediated delayed-type hypersensitivity reactions. These observations suggest a direct association between coagulation and cell-mediated immunity. The cytokine interleukin (IL)-4 potently suppresses cell-mediated immune responses, but its mechanism of action remains to be determined. Herein we demonstrate that the physiologic anticoagulant protein S is IL-4-inducible in primary T cells. Although protein S was known to inhibit the classic factor Va-dependent prothrombinase assembled by endothelial cells and platelets, we found that protein S also inhibits the factor Va-independent prothrombinase assembled by lymphoid cells. Thus, protein S-mediated down-regulation of lymphoid cell procoagulant activity may be one mechanism by which IL-4 antagonizes cell-mediated immunity.
Smiley
S T
ST
Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Boyer
S N
SN
Heeb
M J
MJ
Griffin
J H
JH
Grusby
M J
MJ
D000818:Animals; D000925:Anticoagulants / Q000378:metabolism; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D015943:Factor Va / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008198:Lymph Nodes / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D017293:Protein S / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis
D000925:Anticoagulants; D017931:DNA Primers; D017293:Protein S; D015847:Interleukin-4; D015943:Factor Va; D013925:Thromboplastin