Long-term incubation with IL-4 and IL-10 oppositely modifies procoagulant activity of monocytes and modulates the surface expression of tissue factor and tissue factor pathway inhibitor.
Monocytes can be induced to express both tissue factor (TF) and its inhibitor, TF pathway inhibitor-1 (TFPI-1). A short incubation (<6 h) with interleukin (IL)-4 and IL-10, two potent deactivators of monocyte functions, has been shown to modulate the synthesis and expression of TF by monocytes activated by lipopolysaccharide, but the consequences of longer incubations (up to 96 h) on both TF and TFPI-1 are unknown. The results of this study showed that adherent monocytes in culture spontaneously expressed TF and TFPI and that prolonged incubation with IL-10 induced a time- and dose-dependent decrease of monocyte TF synthesis, and an accumulation of TF/TFPI-1 complexes at the moncyte surface, suggesting a decreased clearance of these complexes. In contrast, IL-4 induced a time- and dose-dependent increase in TF synthesis, which remained intracytoplasmic, as shown by confocal microscopy. Surprisingly, TF:antigen (Ag) was decreased at the monocyte surface, but the procoagulant activity (PCA) of IL-4-treated monocytes was increased, as a result of more pronounced decrease of TFPI-1:Ag expression than that of TF. In conclusion, prolonged incubation with IL-4 and IL-10 oppositely modified PCA of cultured monocytes, and altered TF and TFPI trafficking and clearance. These data explain the respective deleterious or benefit effects of IL-4 or IL-10 in atherothrombosis.
Paysant
Jérôme
J
Laboratoire DIFEMA, UFR de Médecine et Pharmacie de Rouen, Rouen, France.
Soria
Claudine
C
Cornillet-Lefèbvre
Pascale
P
Nguyen
Philippe
P
Lenormand
Bernard
B
Mishal
Zohar
Z
Vannier
Jean-Pierre
JP
Vasse
Marc
M
D000911:Antibodies, Monoclonal / Q000276:immunology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D008074:Lipoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000911:Antibodies, Monoclonal; D001779:Blood Coagulation Factors; D008074:Lipoproteins; D012333:RNA, Messenger; C045071:leukocyte procoagulant activity; C051928:lipoprotein-associated coagulation inhibitor; D016753:Interleukin-10; D015847:Interleukin-4; D013925:Thromboplastin