Monocytes regulate systemic coagulation and inflammation in abdominal sepsis.

Abdominal sepsis is associated with significant changes in systemic inflammation and coagulation. The purpose of this study was to examine the role of peripheral blood monocytes for systemic coagulation, including thrombin generation and consumption of coagulation factors. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Plasma and lung levels of interleukin-6 (IL-6), CXC chemokines (CXCL1, CXCL2 and CXCL5) as well as pulmonary activity of myeloperoxidase (MPO), thrombin generation and coagulation factors were determined 6h after CLP induction. Administration of clodronate liposomes decreased circulating levels of monocytes by 96%. Time to peak thrombin formation was increased and peak and total thrombin generation was decreased in plasma from CLP animals. Monocyte depletion decreased time to peak formation of thrombin and increased peak and total generation of thrombin in septic animals. In addition, monocyte depletion decreased the CLP-induced increase in the levels of thrombin-antithrombin complexes in plasma. Depletion of monocytes increased plasma levels of prothrombin, factor V, factor X, protein C and in septic mice. Moreover, depletion of monocytes decreased CLP-induced levels of IL-6 and CXC chemokines in plasma and lung by more than 59% and 20%, respectively. CLP-induced MPO activity in the lung was attenuated by 44% in animals depleted of monocytes. Taken together, our findings show for the first time that peripheral blood monocytes regulates systemic coagulation and improve our understanding of the pathophysiology of sepsis and encourage further attempts to target innate immune cell functions in abdominal sepsis.