Endothelial cell phagocytosis of senescent neutrophils decreases procoagulant activity

Chunyan Gao; Rui Xie; Wen Li; Jin Zhou; Shuchuan Liu; Fenglin Cao; Yue Liu; Ruishuang Ma; Yu Si; Yan Liu; Yayan Bi; Gary E. Gilbert; Jialan Shi

doi:10.1160/TH12-12-0894

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2013; 109(06): 1079-1090
DOI: 10.1160/TH12-12-0894

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Endothelial cell phagocytosis of senescent neutrophils decreases procoagulant activity

Chunyan Gao

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Rui Xie

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Wen Li^#

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Jin Zhou

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Shuchuan Liu

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Fenglin Cao

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Yue Liu

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Ruishuang Ma

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Yu Si

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Yan Liu

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

,

Yayan Bi

²Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

,

Gary E. Gilbert

³Department of Medicine, VA Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA

,

Jialan Shi

¹Heilongjiang Institute of Hematology and Oncology, Department of Hematology, Harbin, China

³Department of Medicine, VA Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachussetts, USA

› Institutsangaben

Abstract

Summary

Abundant senescent neutrophils traverse the vascular compartment and may contribute to pathologic conditions. For example, they become procoagulant when undergoing apoptosis and may contribute to thrombosis or inflammation. Our previous studies demonstrated a dominant clearance pathway in which the neutrophils can be phagocytosed by liver macrophages. The aim of this study was to explore an alternate pathway of neutrophil clearance by endothelial cells. Phagocytosis of the neutrophils by endothelial cells was performed using various experimental approaches including flow cytometry, confocal microscopy and electron microscopy assays in vitro and in vivo. Procoagulant activity of cultured neutrophils was evaluated by coagulation time, factor Xase and prothrombinase assays. Lactadherin functioned as a novel probe for the detection of phosphatidylserine on apoptotic cells, an opsonin (bridge) between apoptotic cell and phagocyte for promoting phagocytosis, and an efficient anticoagulant for inhibition of factor Xase and thrombin formation. When cultured, purified human neutrophils spontaneously entered apoptosis and developed procoagulant activity that was directly related to the degree of phosphatidylserine exposure. Co-culture of aged neutrophils and endothelial cells resulted in phagocytosis of the neutrophils and prolonged coagulation time. Lactadherin diminished the procoagulant activity and increased the rate of neutrophil clearance. In vivo, neutrophils were sequestered by endothelial cells after blockade of Kupffer cells, a process that was dependent upon both phosphatidylserine exposure and P-selectin expression. Thus, the ability of endothelial cells to clear senescent neutrophils may limit the procoagulant and/or inflammatory impact of these cells.

Keywords

Phagocytosis - endothelial cell - neutrophil - procoagulant activity - lactadherin

Volltext

Referenzen

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