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

Xie, Rui; Gao, Chunyan; Li, Wen; Zhu, Jiuxin; Novakovic, Valerie A.; Wang, Jing; Ma, Ruishuang; Zhou, Jin; Gilbert, Gary E.; Shi, Jialan

doi:10.1182/blood-2011-06-362186

Cited by 45 publications

(45 citation statements)

References 42 publications

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“…For inhibition assays, platelets were preincubated with anti CD62P, anti CD42b, anti CD36, annexin V, or lactadherin followed by co-cultured with ECs at 37 °C for 30 min. Phagocytosis was determined by the percentage of red fluorescence (CMTPX)-positive CMFDA (green) ECs by FACS Canto II flow cytometer 27 .…”

Section: Methodsmentioning

confidence: 99%

“…Engulfment was analyzed using a previous method with some modifications 27 . Briefly, ECs were seeded on glass coverslips coated poly-d-lysine in 12-well culture plates.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, lactadherin acts as a bridge between target cells exposing PS and phagocytes thereby facilitating phagocytosis 26 . Recently, we and others have shown that lactadherin promotes clearance of promyelocytes in acute promyelocytic leukemia and aged erythrocytes and apoptotic cells by angiogenic endothelium 27,28 . Since lactadherin is a readily available specific marker of PS exposure, we examined the role of this molecule in the clearance of activated platelets by ECs in sepsis.…”

Section: Introductionmentioning

confidence: 98%

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Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

Xie

et al. 2017

Sci Rep

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The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

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Section: Methodsmentioning

confidence: 99%

“…Engulfment was analyzed using a previous method with some modifications 27 . Briefly, ECs were seeded on glass coverslips coated poly-d-lysine in 12-well culture plates.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

Xie

et al. 2017

Sci Rep

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“…4A), that work by polymerizing actin, A5 offered the advantage of not restricting cell migration, which can potentially lead to a false identification using stationary particles. Previously, A5 has been used as a phagocytosis inhibitor by binding to the membranous protein phosphatidylserine, interfering with phagocytosis by screening apoptotic cells ( 49 , 51 ). A similar approach is pursued here, using the positively charged A5 protein to nonspecifically bind to the surface of the negatively charged SiNW, effectively screening the SiNWs from internalization (Fig.…”

Section: Resultsmentioning

confidence: 99%

Cellular uptake and dynamics of unlabeled freestanding silicon nanowires

et al. 2016

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“…[76] [151,152] Peritoneal mesothelial cells Limited to subcellular fragments; slow kinetics [72] MSC In vivo in macrophageless mice; slow kinetics Enhanced MSC osteogenic differentiation; increase of CXCR4 and CXCR5 expression, IL-8, CCL2 and CCL5 secretion, as well as Th17 differentiation (via IL-6) [73] [77]…”

Section: Cell Line Hc11mentioning

confidence: 99%

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

2013

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Apoptotic cell removal or interactions of early-stage apoptotic cells with immune cells are associated with an immunomodulatory microenvironment that can be harnessed to exert therapeutic effects. While the involved immune mechanisms are still being deciphered, apoptotic cell infusion has been tested in different experimental models where inflammation is deregulated. This includes chronic and acute inflammatory disorders such as arthritis, contact hypersensitivity and acute myocardial infarction. Apoptotic cell infusion has also been used in transplantation settings to prevent or treat acute and chronic rejection, as well as to limit acute graft-versus-host disease associated with allogeneic hematopoietic cell transplantation. Here, we review the mechanisms involved in apoptotic cell-induced immunomodulation and data obtained in preclinical models of transplantation and inflammatory diseases.

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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 re-

Cited by 45 publications

References 42 publications

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis

Cellular uptake and dynamics of unlabeled freestanding silicon nanowires

Prospects of Apoptotic Cell-Based Therapies for Transplantation and Inflammatory Diseases

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