α2-antiplasmin is associated with macrophage activation and fibrin in a macrophage activation syndrome mouse model

Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated that the roles of α2-antiplasmin (α2AP) in the progression of MAS using fulm...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental immunology 2024-03
Main Authors: Kanno, Yosuke, Toyama, Kinomi, Shibata, Haruna, Matsuo, Osamu, Ozaki, Kei-Ichi
Format: Article
Language:English
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Macrophage activation syndrome (MAS) is a life-threatening condition, characterized by cytopenia, multi-organ dysfunction, and coagulopathy associated with excessive activation of macrophages. In this study, we investigated that the roles of α2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by Toll-like receptor-9 (TLR-9) agonist (CpG) and d-galactosamine (DG). α2AP deficiency attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. Interferon-γ (IFN-γ) is associated with macrophage activation, including migration, and plays a pivotal role in MAS progression. α2AP enhanced the IFN-γ-induced migration, and tissue factor (TF) production. Additionally, we showed that fibrin induced macrophage activation and tumor necrosis factor-α (TNF-α) production. Moreover, the blockade of α2AP by neutralizing antibodies attenuated macrophage accumulation, liver injury, and fibrin deposition in the MAS model mice. These data suggest that α2AP may regulate IFN-γ-induced responses and be associated with macrophage activation and fibrin deposition in the MAS progression.
ISSN:1365-2249