Dilazep and dipyridamole inhibit tissue factor expression on monocytes induced by IgG from patients with...

To investigate whether antiplatelet agents, dilazep and dipyridamole, inhibit tissue factor (TF) expression on monocytes induced by IgG from patients with antiphospholipid syndrome (APS).

Freshly isolated peripheral blood monocytes were allowed to adhere on plastic and then cultured in media containing patient or control antibodies and/or other agonists with or without dilazep or dipyridamole. The TF activity on monocytes was investigated by measuring factor VIIa-dependent generation of factor Xa, using a chromogenic substrate and the TF mRNA expression was examined by real-time PCR (TaqMan PCR).

The TF activity on monocytes induced by APS IgG (250 mg/L) was inhibited by dilazep (0.15-150 micromol/L) and dipyridamole (0.2-200 micromol/L) in a dose-dependent fashion. But, the TF mRNA expression induced by APS IgG was not inhibited. Theophylline (500 micromol/L), an adenosine receptor antagonist, could counteract the inhibitory effect of dilazep and dipyridamole on TF activity.

Antiplatelet agents, dilazep and dipyridamole, block APS IgG-induced monocytes TF expression at a post-transcriptional level, partly by adenosine receptor pathway. Pharmacological agents that block monocytes TF activity, such as dilazep and dipyridamole, are a novel therapeutic approach in APS.