The pathogenesis of chronic spontaneous urticaria (CSU) has been considered to be associated with the activation of the extrinsic blood coagulation cascade. However, the trigger of the extrinsic coagulation cascade in patients with CSU remains unclear. We previously reported that histamine and lipopolysaccharide (LPS) synergistically induced the expression of tissue factor (TF) by human umbilical vein endothelial cells (HUVECs). It develops inter-cellular gap formation of HUVECs via the activation of extrinsic coagulation cascade. Moreover, monocytes in peripheral blood may also express TF in a certain condition.
We here investigated the levels of TF expression on peripheral monocytes of patients with CSU by means of flow cytometry and RT-PCR. The activity of TF on monocytes was evaluated by ACTICHROME® TF assay. The formation of inter-cellular gaps of HUVECs was monitored by impedance analysis.
The levels of TF expression on monocytes of patients with CSU were significantly higher than those of healthy donors. Moreover, the expression of TF mRNA, surface protein of TF and TF activity on monocytes were enhanced by the treatment with LPS. Furthermore, inter-cellular gap formation of HUVECs was induced in the presence of plasma and TF-expressing monocytes treated with LPS. 
We demonstrated that TF expression on monocytes of patients with CSU was enhanced and that TF expressed on monocytes drives inter-cellular gap formation of vascular endothelial cells via the extrinsic blood coagulation cascade. This phenomenon may contribute to the pathogenesis of severe and refractory CSU.

Tissue factor expressed on monocytes induces inter-cellular gap formation of vascular endothelial cells via the extrinsic blood coagulation cascade