Megakaryocyte NLRP3 hyperactivation induces anemia and potentiates inflammatory response in mice
Research Square (Research Square)(2023)
摘要
Abstract The NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome has been described in both immune cells and platelets but its role in the megakaryocyte (MK) lineage remains elusive. Here, we generated Nlrp3 A350V/+ / Gp1ba -Cre KI/+ mice carrying MK/platelet-specific mutation associated with human Muckle-Wells syndrome. Platelets from these mice expressed elevated levels of both precursor and active form of caspase-1 suggesting hyperactivity of NLRP3 inflammasome. Nlrp3 A350V/+ / Gp1ba -Cre KI/+ mice developed normally and had normal platelet counts. Expression of major platelet receptors, platelet functions, and venous thrombosis were unchanged. Nlrp3 A350V/+ / Gp1ba -Cre KI/+ mice had mild anemia, reduced Ter119+ cells in the bone marrow, and splenomegaly. A mild increase in MK TGF-β1 might be involved in the anemic phenotype. Zymosan stimulation in Nlrp3 A350V/+ / Gp1ba -Cre KI/+ mice induced increased neutrophil egression and levels of a set of proinflammatory cytokines, IL-10 and G-CSF in the peritoneal fluid. Thus, MK/platelet NLRP3 promotes the acute inflammatory response and its hyperactivation leads to mild anemia and increased extramedullary erythropoiesis.
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关键词
inflammatory response,anemia
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