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Impaired Hematopoiesis and Disrupted Monocyte/Macrophage Homeostasis in Mucopolysaccharidosis Type I Mice
Author(s) -
Viana Gustavo Monteiro,
Buri Marcus Vinícius,
ParedesGamero Edgar Julian,
Martins Ana Maria,
D'Almeida Vânia
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25120
Subject(s) - haematopoiesis , microbiology and biotechnology , mucopolysaccharidosis type i , progenitor cell , biology , immunology , macrophage , myeloid , monocyte , lysosomal storage disease , mucopolysaccharidosis , stem cell , chemistry , medicine , biochemistry , enzyme replacement therapy , disease , in vitro , enzyme
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. J. Cell. Physiol. 231: 698–707, 2016. © 2015 Wiley Periodicals, Inc.