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Hepcidin independent iron recycling in a mouse model of β‐thalassaemia intermedia
Author(s) -
Frazer David M.,
Wilkins Sarah J.,
Mirciov Cornel S. G.,
Dunn Linda A.,
Anderson Gregory J.
Publication year - 2016
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.14206
Subject(s) - hepcidin , ferroportin , erythropoiesis , endocrinology , medicine , macrophage , serum iron , spleen , iron deficiency , in vivo , biology , chemistry , immunology , anemia , in vitro , biochemistry , microbiology and biotechnology
Summary In conditions such as β‐thalassaemia, stimulated erythropoiesis can reduce the expression of the iron regulatory hormone hepcidin, increasing both macrophage iron release and intestinal iron absorption and leading to iron loading. However, in certain conditions, sustained elevation of erythropoiesis can occur without an increase in body iron load. To investigate this in more detail, we made use of a novel mouse strain ( RBC 14 ), which exhibits mild β‐thalassaemia intermedia with minimal iron loading. We compared iron homeostasis in RBC 14 mice to that of Hbb th3/+ mice, a more severe model of β‐thalassaemia intermedia. Both mouse strains showed a decrease in plasma iron half‐life, although the changes were less severe in RBC 14 mice. Despite this, intestinal ferroportin and serum hepcidin levels were unaltered in RBC 14 mice. In contrast, Hbb th3/+ mice exhibited reduced serum hepcidin and increased intestinal ferroportin. However, splenic ferroportin levels were increased in both mouse strains. These data suggest that in low‐grade chronic haemolytic anaemia, such as that seen in RBC 14 mice, the increased erythroid iron requirements can be met through enhanced macrophage iron release without the need to increase iron absorption, implying that hepcidin is not the sole regulator of macrophage iron release in vivo .