| Abstract |
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 the roles of alpha2-antiplasmin (α2AP) in the progression of MAS using fulminant MAS mouse model induced by toll-like receptor-9 agonist (CpG) and D-(+)-galactosamine hydrochloride (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 production. Additionally, we showed that fibrin-induced macrophage activation and tumor necrosis factor-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.
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