M1-macrophage polarization is upregulated in deep vein thrombosis and contributes to the upregulation of adhesion molecules.

Deep vein thrombosis (DVT) is characterized by high acute fatality rate due to pulmonary embolism and by serious long-term complications. The risk of DVT development is increased in many medical conditions, such as trauma, cancer, and surgery. However, DVT can also occur as an idiopathic disease without clearly identifiable causes. To investigate the pathogenesis of idiopathic DVT, the involvement of circulating monocytes and macrophages was examined. Data showed that circulating monocytes and monocyte-derived macrophages from DVT patients presented significantly elevated M1-polarization, characterized by higher IL-6 and higher TNF-α than corresponding cells from controls. Macrophages from DVT patients were more potent at stimulating endothelial cell-mediated expression of adhesion molecules, including SELE, ICAM1, and VCAM1, than macrophages from controls. M1-polarization, but not M2-polarization, could profoundly upregulate the expression of adhesion molecules. This upregulation was dependent on direct cell-to-cell contact, as well as on contact-independent TNF-α expression. IL-10 expression, on the other hand, significantly reduced the upregulation of adhesion molecules. Together, this study demonstrated that circulating monocytes and macrophages could contribute to the pathogenesis of idiopathic DVT.