title: Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice.
abstract: Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disease caused by alpha-L-iduronidase deficiency in which heparan and dermatan sulfate degradation is compromised. Besides primary lysosomal glycosaminoglycan accumulation, further changes in cellular functions have also been described in several murine MPS models. Herein, we evaluated alterations in hematopoiesis and its implications on the production of mature progeny in a MPS I murine model. Despite the significant increase in hematopoietic stem cells, a reduction in common myeloid progenitors and granulocyte-macrophage progenitor cells was observed in Idua -/- mice bone marrow. Furthermore, no alterations in number, viability nor activation of cell death mechanisms were observed in Idua -/- mice mature macrophages but they presented higher sensitivity to apoptotic induction after staurosporine treatment. In addition, changes in Ca(2+) signaling and a reduction in phagocytosis ability were also found. In summary, our results revealed significant intracellular changes in mature Idua -/- macrophages related to alterations in Idua -/- mice hematopoiesis, revealing a disruption in cell homeostasis. These results provide new insights into physiopathology of MPS I.
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Gustavo Monteiro
authors.initials: GM
authors.lastname: Viana
authors.affiliation: Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marcus Vinícius
authors.initials: MV
authors.lastname: Buri
authors.affiliation: Department of Biochemistry, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.|Centro Interdisciplinar de Investigação Bioquímica, Universidade de Mogi das Cruzes, Mogi das Cruzes, São Paulo, Brazil.
authors.forename: Edgar Julian
authors.initials: EJ
authors.lastname: Paredes-Gamero
authors.affiliation: Centro de Referência de Erros Inatos do Metabolismo (CREIM), Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
authors.affiliation: Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.|Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
mesh_terms: D000818:Animals; D016923:Cell Death / Q000235:genetics; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D006410:Hematopoiesis / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D008059:Mucopolysaccharidosis I / Q000235:genetics* / Q000378:metabolism*