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نوع المنشور

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النص الكامل

تحميل

Macrophage activation syndrome (MAS) is a life-threatening disorder characterized by

a cytokine storm and multiorgan dysfunction due to excessive immune activation.

Althoughabnormalities of coagulationandfibrinolysis are majorcomponentsofMAS,the

role of the fibrinolytic system and its key player, plasmin, in the development of MAS

remains to be solved. We established a murine model of fulminant MAS by repeated

injections of Toll-like receptor-9 (TLR-9) agonist and D-galactosamine (DG) in immunocompetent

mice. We found plasmin was excessively activated during the progression of

fulminant MAS in mice. Genetic and pharmacological inhibition of plasmin counteracted

MAS-associated lethality and other related symptoms. We show that plasmin regulates

the influx of inflammatory cells and the production of inflammatory cytokines/chemokines.

Collectively, our findings identify plasmin as a decisive checkpoint in the inflammatory

response during MAS and a potential novel therapeutic target for MAS

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