Dexamethasone Induce THP-1cells Release Procoagulant Tissue Factor(+)-microparticles

Objective:This study was designed to investigate the number of total microparticles and TF(+)-microparticles induced by corticosteroids in monocyte, microparticle-associated procoagulant activity, and the TF gene expression.Material and Methods:THP-1cells cultured with dexamethasone in different concentrations (0.1mM/0.01mM/0.001mM), and for different time (4hours/12hours/24hours). The number of total microparticles and TF(+)-microparticles in the supernatant were counted with flow cytometry analysis. The whole supernatant procoagulant activity was measured by one-stage recalcifiction assay. Microparticles were captured by CD14antibodies, and TF activity of these microparticles was measured with modified ELISA. TF-mRNA was detected by realtime-PCR.Results:Dexamethasone induce THP-1release TF(+)-microparticles1.5-3fold over baseline, and total microparticles1.3-2.5fold over baseline. Dexamethasone dosage was correlated with the number of TF(+)-microparticles(r=0.673, p<0.001), and also highly with the number of total microparticles (r=0.804, p=0.001). These TF(+)-microparticles captured by CD14antibody display a procoagulant activity. Dexamethasone doesn’t enhance the induction of releasing microparticles by LPS.The cloting time of supernatant induced by dexamethasone was significantly short than negative control.4h and24h cloting time of supernatant was negatively correlated with the number of TF(+)-microparticles in supernatant(4h r=-0.762p=0.028;12hr=-0.833p=0.010). At4h, dexamethasone can significantly reduce TF-mRNA (p<0.01). But0.01mM dexamethasone can increase TF-mRNA at12h and24h. There is no evidence of correlation between TF-mRNA and the supernatant procoagulant activity.Conclusion:Dexamethasone can induce THP-1cells release TF(+)-microparticles, which have procoagulant activity in vitro. The number of TF(+)-microparticles was correlated with the dosage of dexamethasone, and the whole supernatant procoagulant activity. This effect is noot due to regulation of TF expression by dexamethasone.