マクロファージと凝固・線溶異常

Abstract

We examined the role of monocyte-macrophages (MO/MAC) in hemostatic disorder. Plasma cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF) were higher in patients with hemophagocytic syndrome (HPS) associated severe hemostatic disorder and organ failure. These cytokine levels were also increased in patients with disseminated intravascular coagulation (DIC), suggesting that the activation of MO/MAC is involved in the pathogenesis of hemostatic disorder.Tissue factor (TF) activity and plasminogen activator (PA) activity in leukemic cells were significantly higher in DIC patients than in non DIC patients. PA inhibitor-II antigen in leukemic cells was highest in acute monocytic or myelomonocytic leukemia (AMoL/AMMoL). Those patients showed hypercoagulant-hypofibrinolytic state and organ failure, suggesting that PAT-II played an important role in the hemostatic abnormalities.In the study of cultured MO/MAC, IL-1β elevated TF activity and PAI-II antigen in MO/MAC lysate, their culture medium significantly elevated TF and PAI-I production of human umbilical vein endothelial cells (HUVEC). Lipoproteins also had the capacity to elevate TF production of MO/MAC.These finding suggested that MO/MAC play a very important role in thrombogenesis and organ failure by secretion of cytokines and/or expression of TF and PAI-II.