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Article: Mice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome

TitleMice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome
Authors
KeywordsMacrophage
Hematopoiesis
Legumain
Lysosomal disorder
Issue Date2009
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 2, p. 468-473 How to Cite?
AbstractAsparaginyl endopeptidase (AEP or legumain) is a lysosomal cysteine protease that cleaves protein substrates on the C-terminal side of asparagine. AEP plays a pivotal role in the endosome/lysosomal degradation system and is implicated in antigen processing. The processing of the lysosomal proteases cathepsins in kidney is completely defective in AEP-deficient mice with accumulation of macromolecules in the lysosomes, which is typically seen in lysosomal disorders. Here we show that mutant mice lacking AEP develop fever, cytopenia, hepatosplenomegaly, and hemophagocytosis, which are primary pathological manifestations of hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HLH). Moreover, AEP deficiency provokes extramedullary hematopoiesis in the spleen and abnormally enlarged histiocytes with ingested red blood cells (RBCs) in bone marrow. Interestingly, RBCs from AEP-null mice are defective in plasma membrane components. Further, AEP-null mice display lower natural killer cell activity, but none of the major cytokines is substantially abnormal. These results indicate that AEP might be a previously unrecognized component in HLH pathophysiology. © 2008 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/225076
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
Errata

 

DC FieldValueLanguage
dc.contributor.authorChan, Chi Bun-
dc.contributor.authorAbe, Michiyo-
dc.contributor.authorHashimoto, Noriyoshi-
dc.contributor.authorHao, Chunhai-
dc.contributor.authorWilliams, Ifor R.-
dc.contributor.authorLiu, Xia-
dc.contributor.authorNakao, Shinji-
dc.contributor.authorYamamoto, Akitsugu-
dc.contributor.authorLi, Shi Yong-
dc.contributor.authorHara-Nishimura, Ikuko-
dc.contributor.authorAsano, Masahide-
dc.contributor.authorYe, Keqiang-
dc.date.accessioned2016-04-18T11:16:42Z-
dc.date.available2016-04-18T11:16:42Z-
dc.date.issued2009-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2009, v. 106, n. 2, p. 468-473-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/225076-
dc.description.abstractAsparaginyl endopeptidase (AEP or legumain) is a lysosomal cysteine protease that cleaves protein substrates on the C-terminal side of asparagine. AEP plays a pivotal role in the endosome/lysosomal degradation system and is implicated in antigen processing. The processing of the lysosomal proteases cathepsins in kidney is completely defective in AEP-deficient mice with accumulation of macromolecules in the lysosomes, which is typically seen in lysosomal disorders. Here we show that mutant mice lacking AEP develop fever, cytopenia, hepatosplenomegaly, and hemophagocytosis, which are primary pathological manifestations of hemophagocytic syndrome/hemophagocytic lymphohistiocytosis (HLH). Moreover, AEP deficiency provokes extramedullary hematopoiesis in the spleen and abnormally enlarged histiocytes with ingested red blood cells (RBCs) in bone marrow. Interestingly, RBCs from AEP-null mice are defective in plasma membrane components. Further, AEP-null mice display lower natural killer cell activity, but none of the major cytokines is substantially abnormal. These results indicate that AEP might be a previously unrecognized component in HLH pathophysiology. © 2008 by The National Academy of Sciences of the USA.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectMacrophage-
dc.subjectHematopoiesis-
dc.subjectLegumain-
dc.subjectLysosomal disorder-
dc.titleMice lacking asparaginyl endopeptidase develop disorders resembling hemophagocytic syndrome-
dc.typeArticle-
dc.description.natureLink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0809824105-
dc.identifier.pmid19106291-
dc.identifier.scopuseid_2-s2.0-58849134849-
dc.identifier.volume106-
dc.identifier.issue2-
dc.identifier.spage468-
dc.identifier.epage473-
dc.identifier.eissn1091-6490-
dc.relation.erratumeid:eid_2-s2.0-78650760737-

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