Histidine-rich glycoprotein stimulates human neutrophil phagocytosis and prolongs survival through CLEC1A

Yohei Takahashi, Hidenori Wake, Masakiyo Sakaguchi, Yukinori Yoshii, Kiyoshi Teshigawara, Dengli Wang, Masahiro Nishibori

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13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)737-750
Number of pages14
JournalJournal of Immunology
Issue number4
Publication statusPublished - Feb 15 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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