Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice

Autor(es)

Viana, Gustavo Monteiro ^[1] ; Buri, Marcus Vinicius ^[2] ; Paredes-Gamero, Edgar Julian ^{[3, 2]} ; Martins, Ana Maria ^[4] ; D'Almeida, Vania ^{[5, 1]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Pediat, Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Biochem, Sao Paulo, SP - Brazil

^[3] Univ Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, Mogi Das Cruzes, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Pediat, Ctr Referencia Erros Inatos Metab, Sao Paulo, SP - Brazil

^[5] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 231, n. 3, p. 698-707, MAR 2016.
• Citações Web of Science: 5

Resumo

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 Ca2+ 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. J. Cell. Physiol. 231: 698-707, 2016. (c) 2015 Wiley Periodicals, Inc. (AU)

• Processo FAPESP: 11/18050-9 - Investigação de alterações na homeostase celular em camundongos com mucopolissacaridose tipo I
• Beneficiário: Vânia D'Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 10/10458-6 - Investigação de alterações na homeostase celular de fibroblastos e hepatócitos de camundongos com Mucopolissacaridose tipo I.
• Beneficiário: Gustavo Monteiro Viana
• Modalidade de apoio: Bolsas no Brasil - Doutorado