TY - JOUR
T1 - Histidine-rich glycoprotein stimulates human neutrophil phagocytosis and prolongs survival through CLEC1A
AU - Takahashi, Yohei
AU - Wake, Hidenori
AU - Sakaguchi, Masakiyo
AU - Yoshii, Yukinori
AU - Teshigawara, Kiyoshi
AU - Wang, Dengli
AU - Nishibori, Masahiro
N1 - Funding Information:
This work was supported by the Japan Agency for Medical Research and Development (JP19im0210109) and the Japan Society for the Promotion of Science (17K15580).
Publisher Copyright:
Copyright © 2021 by The American Association of Immunologists, Inc.
PY - 2021/2/15
Y1 - 2021/2/15
N2 - Histidine-rich glycoprotein (HRG) is a multifunctional plasma protein and maintains the homeostasis of blood cells and vascular endothelial cells. In the current study, we demonstrate that HRG and recombinant HRG concentration dependently induced the phagocytic activity of isolated human neutrophils against fluorescence-labeled Escherichia coli and Staphylococcus aureus through the stimulation of CLEC1A receptors, maintaining their spherical round shape. The phagocytosis-inducing effects of HRG were inhibited by a specific anti-HRG Ab and enhanced by opsonization of bacteria with diluted serum. HRG and C5a prolonged the survival time of isolated human neutrophils, in association with a reduction in the spontaneous production of extracellular ROS. In contrast, HRG maintained the responsiveness of neutrophils to TNF-a, zymosan, and E. coli with regard to reactive oxygen species production. The blocking Ab for CLEC1A and recombinant CLEC1A-Fc fusion protein significantly inhibited the HRG-induced neutrophil rounding, phagocytic activity, and prolongation of survival time, suggesting the involvement of the CLEC1A receptor in the action of HRG on human neutrophils. These results as a whole indicated that HRG facilitated the clearance of E. coli and S. aureus by maintaining the neutrophil morphology and phagocytosis, contributing to the antiseptic effects of HRG in vivo.
AB - Histidine-rich glycoprotein (HRG) is a multifunctional plasma protein and maintains the homeostasis of blood cells and vascular endothelial cells. In the current study, we demonstrate that HRG and recombinant HRG concentration dependently induced the phagocytic activity of isolated human neutrophils against fluorescence-labeled Escherichia coli and Staphylococcus aureus through the stimulation of CLEC1A receptors, maintaining their spherical round shape. The phagocytosis-inducing effects of HRG were inhibited by a specific anti-HRG Ab and enhanced by opsonization of bacteria with diluted serum. HRG and C5a prolonged the survival time of isolated human neutrophils, in association with a reduction in the spontaneous production of extracellular ROS. In contrast, HRG maintained the responsiveness of neutrophils to TNF-a, zymosan, and E. coli with regard to reactive oxygen species production. The blocking Ab for CLEC1A and recombinant CLEC1A-Fc fusion protein significantly inhibited the HRG-induced neutrophil rounding, phagocytic activity, and prolongation of survival time, suggesting the involvement of the CLEC1A receptor in the action of HRG on human neutrophils. These results as a whole indicated that HRG facilitated the clearance of E. coli and S. aureus by maintaining the neutrophil morphology and phagocytosis, contributing to the antiseptic effects of HRG in vivo.
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U2 - 10.4049/jimmunol.2000817
DO - 10.4049/jimmunol.2000817
M3 - Article
C2 - 33452125
AN - SCOPUS:85100453079
VL - 206
SP - 737
EP - 750
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 4
ER -