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The bone marrow hematopoietic microenvironment is impaired in iron-overloaded mice.
Okabe, Hiroshi; Suzuki, Takahiro; Uehara, Eisuke; Ueda, Masuzu; Nagai, Tadashi; Ozawa, Keiya.
Afiliação
  • Okabe H; Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Eur J Haematol ; 93(2): 118-28, 2014 Aug.
Article em En | MEDLINE | ID: mdl-24628561
ABSTRACT

OBJECTIVES:

Increasing numbers of reports have described hematopoietic improvement after iron chelation therapy in iron-overloaded patients. These observations indicate that excess iron could affect hematopoiesis unfavorably. To investigate how excess iron affects hematopoiesis in vivo, we generated iron-overloaded mice and examined hematopoietic parameters in these mice.

METHODS:

We generated iron-overloaded mice by injecting 200 mg of iron dextran into C57BL/6J mice, and immature hematopoietic cells in the bone marrow were evaluated by flow cytometric analyses, colony-forming assays, and bone marrow transplantation analyses. We also examined changes in molecular profiles of the hematopoietic microenvironment. RESULTS AND

CONCLUSIONS:

Iron-overloaded (IO) mice did not show significant defects in the hematopoietic data of the peripheral blood. Myeloid progenitor cells in the bone marrow were increased in IO mice, but the number and function of the erythroid progenitors and hematopoietic stem cells were not significantly affected. However, bone marrow transplantation from normal donors to IO recipients showed delayed hematopoietic reconstitution, which indicates that excess iron impacts the hematopoietic microenvironment negatively. Microarray and quantitative RT-PCR analyses on the bone marrow stromal cells demonstrated remarkably reduced expression of CXCL12, VCAM-1, Kit-ligand, and IGF-1 in the iron-overloaded mice. In addition, erythropoietin and thrombopoietin levels were significantly suppressed, and increased oxidative stress was observed in the IO bone marrow and liver. Consequently, our findings indicate that excess iron can damage bone marrow stromal cells and other vital organs, disrupting hematopoiesis presumably by increased oxidative stress.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Medula Óssea / Células da Medula Óssea / Sobrecarga de Ferro / Células-Tronco Mesenquimais / Microambiente Celular / Fígado Limite: Animals Idioma: En Revista: Eur J Haematol Assunto da revista: HEMATOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Medula Óssea / Células da Medula Óssea / Sobrecarga de Ferro / Células-Tronco Mesenquimais / Microambiente Celular / Fígado Limite: Animals Idioma: En Revista: Eur J Haematol Assunto da revista: HEMATOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Japão