A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin.

Blood
Airie KimTomas Ganz

Abstract

Anemia is a common complication of infections and inflammatory diseases, but the few mouse models of this condition are not well characterized. We analyzed in detail the pathogenesis of anemia induced by an injection of heat-killed Brucella abortus and examined the contribution of hepcidin by comparing wild-type (WT) to iron-depleted hepcidin-1 knockout (Hamp-KO) mice. B abortus-treated WT mice developed severe anemia with a hemoglobin nadir at 14 days and partial recovery by 28 days. After an early increase in inflammatory markers and hepcidin, WT mice manifested hypoferremia, despite iron accumulation in the liver. Erythropoiesis was suppressed between days 1 and 7, and erythrocyte destruction was increased as evidenced by schistocytes on blood smears and shortened red blood cell lifespan. Erythropoietic recovery began after 14 days but was iron restricted. In B abortus-treated Hamp-KO compared with WT mice, anemia was milder, not iron restricted, and had a faster recovery. Similarly to severe human anemia of inflammation, the B abortus model shows multifactorial pathogenesis of inflammatory anemia including iron restriction from increased hepcidin, transient suppression of erythropoiesis, and shortened erythrocyte lifespan. ...Continue Reading

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Citations

Feb 21, 2014·Trends in Pharmacological Sciences·Piotr Ruchala, Elizabeta Nemeth
Apr 1, 2014·PloS One·Airie KimTomas Ganz
Jul 30, 2014·Hematology/oncology Clinics of North America·Elizabeta Nemeth, Tomas Ganz
Nov 29, 2015·Experimental Hematology·Ana Cordeiro Gomes, Maria Salomé Gomes
Oct 16, 2015·Nature Reviews. Cardiology·Nicholas W MorrellKenneth D Bloch
Nov 26, 2015·Blood Cells, Molecules & Diseases·Airie KimTomas Ganz
Feb 24, 2015·Immunological Reviews·Günter Weiss, Ulrich E Schaible
May 16, 2015·International Journal of Laboratory Hematology·J Arezes, E Nemeth
Jul 15, 2015·Nature Reviews. Immunology·Tomas Ganz, Elizabeta Nemeth
Feb 18, 2016·Current Opinion in Hematology·Chia-Yu Wang, Jodie L Babitt
Feb 25, 2015·Current Opinion in Hematology·Airie Kim, Elizabeta Nemeth
Feb 22, 2014·Blood·Paula G Fraenkel
May 9, 2014·Frontiers in Pharmacology·Maura PoliPaolo Arosio
May 6, 2014·Frontiers in Pharmacology·Fabiana BustiDomenico Girelli
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May 10, 2017·The Journal of Veterinary Medical Science·Rehab Marray NsreldenShuichi Furusawa
Nov 3, 2016·American Journal of Physiology. Renal Physiology·Oleh AkchurinStefano Rivella
Nov 18, 2017·International Journal of Hematology·Tomas Ganz
Jan 5, 2019·PLoS Computational Biology·Jignesh H Parmar, Pedro Mendes
Feb 7, 2019·American Journal of Physiology. Renal Physiology·Kyle A BauckmanIndira U Mysorekar
Feb 28, 2018·BMC Physiology·Inka GallitzAndrea U Steinbicker
Oct 14, 2016·American Journal of Physiology. Renal Physiology·Mark R HanudelIsidro B Salusky
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Sep 19, 2019·The New England Journal of Medicine·Tomas Ganz
Oct 30, 2019·The Journal of Clinical Investigation·Veena SangkhaeElizabeta Nemeth
May 20, 2020·Journal of Neuroscience Research·Shangru LyuYuqing Li
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Jun 16, 2017·The Journal of Biological Chemistry·Richard Coffey, Tomas Ganz
Jul 1, 2020·Physiological Reports·Vida ZhangAirie Kim

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