title: Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells.
abstract: 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 phosphatidylserine-exposed target APL cells was time-dependently decreased after incubation with phagocytes (THP-1-derived macrophages or HUVECs). Thrombin production on target APL cells was reduced by 40%-45% after 2 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 2 hours of phagocytosis and ∼ 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.
authors.affiliation: Health Ministry Key Laboratory of Cell Transplantation, Heilongjiang Institute of Hematology and Oncology, Department of Hematology, The First Affiliated Hospital, Harbin Medical University, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xie
authors.forename: Chunyan
authors.initials: C
authors.lastname: Gao
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Jiuxin
authors.initials: J
authors.lastname: Zhu
authors.forename: Valerie
authors.initials: V
authors.lastname: Novakovic
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ruishuang
authors.initials: R
authors.lastname: Ma
authors.forename: Jin
authors.initials: J
authors.lastname: Zhou
authors.forename: Gary E
authors.initials: GE
authors.lastname: Gilbert
authors.forename: Jialan
authors.initials: J
authors.lastname: Shi
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism; D001777:Blood Coagulation; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008875:Middle Aged; D008894:Milk Proteins / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; C098942:MFGE8 protein, human; D008894:Milk Proteins; D010718:Phosphatidylserines; D013925:Thromboplastin; D013917:Thrombin; D015951:Factor Xa; D005341:Fibrinolysin