Blood：周晋等提出亚砷酸抗白血病给药新方式

Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells

Rui Xie1, Chunyan Gao1, Wen Li1, Jiuxin Zhu1, Valerie Novakovic2, Jing Wang1, Ruishuang Ma1, Jin Zhou1, Gary E. Gilbert2, and Jialan Shi2,*

The coagulopathy of acute promyelocytic leukemia (APL) is mainly related to procoagulant substances and fibrinolytic activators of APL blasts, but the fate of these leukemic cells is unknown. The aim of this study was to investigate the removal of APL blasts by macrophages and endothelial cells in vitro and consequent procoagulant and fibrinolytic activity of APL cells. We found that human umbilical vein endothelial cells as well as THP-1 and monocyte-derived macrophages bound, engulfed and subsequently degraded immortalized APL cell line NB4 and primary APL cells. Lactadherin promoted phagocytosis of APL cells in a time-dependent fashion. Furthermore, factor Xa and prothrombinase activity of PS-exposed target APL cells was time-dependently decreased after incubation with phagocytes (THP-1-derived macrophages or human umbilical vein endothelial cells). Thrombin production on target APL cells was reduced by 40-45% after two hours of coincubation with phagocytes, and 80% by a combination of lactadherin and phagocytes. Moreover, plasmin generation of target APL cells was inhibited 30% by two hours of phagocytosis, and approximately 50% by lactadherin-mediated engulfment. These results suggest that engulfment by macrophages and endothelial cells reduce procoagulant and fibrinolytic activity of APL blasts. Lactadherin and phagocytosis could cooperatively ameliorate the clotting disorders in APL.