Effects of Histidine-rich glycoprotein on erythrocyte aggregation and hemolysis

Implications for a role under septic conditions

Hui Zhong, Hidenori Wake, Keyue Liu, Yuan Gao, Kiyoshi Teshigawara, Masakiyo Sakaguchi, Shuji Mori, Masahiro Nishibori

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells. In the present study, we subjected isolated erythrocytes to Zn2+ stimulation, which activated their aggregation and PS expression. We then determined the Zn2+ contents in septic lung and kidney tissues, and found that they were elevated, suggesting that eryptosis was enhanced in these tissues. Erythrocyte adhesion to endothelial cells was also significantly increased after Zn2+ stimulation, and this effect was inhibited by HRG. Finally, we examined HRG treatment in septic model mice, and found that HRG decreased hemolysis, possibly due to its ability to bind heme. Our study demonstrated a novel Zn2+-initiated aggregation/thrombus formation pathway. We also showed the regulatory role of HRG in this pathway, together with the ability of HRG to inhibit hemolysis under septic conditions. HRG supplementation might be a novel therapeutic strategy for inflammatory disorders, especially sepsis.

Original languageEnglish
Pages (from-to)97-106
Number of pages10
JournalJournal of Pharmacological Sciences
Volume136
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

Erythrocyte Aggregation
Hemolysis
Phosphatidylserines
Erythrocytes
Sepsis
Endothelial Cells
histidine-rich proteins
Heme
Neutrophils
Thrombosis
Macrophages
Kidney
Lung
Membranes

Keywords

  • Aggregation
  • Eryptosis
  • Hemolysis
  • Histidine-rich glycoprotein (HRG)
  • Sepsis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

@article{e06bf6c658434627b8213184b3cc2d5a,
title = "Effects of Histidine-rich glycoprotein on erythrocyte aggregation and hemolysis: Implications for a role under septic conditions",
abstract = "The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells. In the present study, we subjected isolated erythrocytes to Zn2+ stimulation, which activated their aggregation and PS expression. We then determined the Zn2+ contents in septic lung and kidney tissues, and found that they were elevated, suggesting that eryptosis was enhanced in these tissues. Erythrocyte adhesion to endothelial cells was also significantly increased after Zn2+ stimulation, and this effect was inhibited by HRG. Finally, we examined HRG treatment in septic model mice, and found that HRG decreased hemolysis, possibly due to its ability to bind heme. Our study demonstrated a novel Zn2+-initiated aggregation/thrombus formation pathway. We also showed the regulatory role of HRG in this pathway, together with the ability of HRG to inhibit hemolysis under septic conditions. HRG supplementation might be a novel therapeutic strategy for inflammatory disorders, especially sepsis.",
keywords = "Aggregation, Eryptosis, Hemolysis, Histidine-rich glycoprotein (HRG), Sepsis",
author = "Hui Zhong and Hidenori Wake and Keyue Liu and Yuan Gao and Kiyoshi Teshigawara and Masakiyo Sakaguchi and Shuji Mori and Masahiro Nishibori",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.jphs.2017.11.003",
language = "English",
volume = "136",
pages = "97--106",
journal = "Journal of Pharmacological Sciences",
issn = "1347-8648",
publisher = "The Japanese Pharmacological Society",
number = "3",

}

TY - JOUR

T1 - Effects of Histidine-rich glycoprotein on erythrocyte aggregation and hemolysis

T2 - Implications for a role under septic conditions

AU - Zhong, Hui

AU - Wake, Hidenori

AU - Liu, Keyue

AU - Gao, Yuan

AU - Teshigawara, Kiyoshi

AU - Sakaguchi, Masakiyo

AU - Mori, Shuji

AU - Nishibori, Masahiro

PY - 2018/3/1

Y1 - 2018/3/1

N2 - The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells. In the present study, we subjected isolated erythrocytes to Zn2+ stimulation, which activated their aggregation and PS expression. We then determined the Zn2+ contents in septic lung and kidney tissues, and found that they were elevated, suggesting that eryptosis was enhanced in these tissues. Erythrocyte adhesion to endothelial cells was also significantly increased after Zn2+ stimulation, and this effect was inhibited by HRG. Finally, we examined HRG treatment in septic model mice, and found that HRG decreased hemolysis, possibly due to its ability to bind heme. Our study demonstrated a novel Zn2+-initiated aggregation/thrombus formation pathway. We also showed the regulatory role of HRG in this pathway, together with the ability of HRG to inhibit hemolysis under septic conditions. HRG supplementation might be a novel therapeutic strategy for inflammatory disorders, especially sepsis.

AB - The apoptotic process of erythrocytes is known as eryptosis, and is characterized by phosphatidylserine (PS) expression on the outer membrane. PS-positive erythrocytes are increased in sepsis, and PS is believed to facilitate coagulation of erythrocytes and activate macrophages. However, the relationship between eryptosis and abnormal coagulation in sepsis is still not fully understood. Histidine-rich glycoprotein (HRG) inhibits immunothrombus formation by regulating neutrophils and vascular endothelial cells. In the present study, we subjected isolated erythrocytes to Zn2+ stimulation, which activated their aggregation and PS expression. We then determined the Zn2+ contents in septic lung and kidney tissues, and found that they were elevated, suggesting that eryptosis was enhanced in these tissues. Erythrocyte adhesion to endothelial cells was also significantly increased after Zn2+ stimulation, and this effect was inhibited by HRG. Finally, we examined HRG treatment in septic model mice, and found that HRG decreased hemolysis, possibly due to its ability to bind heme. Our study demonstrated a novel Zn2+-initiated aggregation/thrombus formation pathway. We also showed the regulatory role of HRG in this pathway, together with the ability of HRG to inhibit hemolysis under septic conditions. HRG supplementation might be a novel therapeutic strategy for inflammatory disorders, especially sepsis.

KW - Aggregation

KW - Eryptosis

KW - Hemolysis

KW - Histidine-rich glycoprotein (HRG)

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=85043367391&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043367391&partnerID=8YFLogxK

U2 - 10.1016/j.jphs.2017.11.003

DO - 10.1016/j.jphs.2017.11.003

M3 - Article

VL - 136

SP - 97

EP - 106

JO - Journal of Pharmacological Sciences

JF - Journal of Pharmacological Sciences

SN - 1347-8648

IS - 3

ER -