EXACERBATED HEMOLYTIC ANEMIA WITH EXPOSURE TO PHENYLHYDRAZINE IN HRI DEFICIENCY
Phenylhydrazine (PHZ) exposure may cause adverse health issues via inhalation, ingestion, or dermal or eye contact. PHZ has been documented to cause severe hemolytic anemia, degenerative lesions in livers and kidneys and lung tumors in animals or humans. Heme-regulated eIF2α kinase (HRI) plays an essential protective role in anemias of iron deficiency, erythroid protoporphyria, and β-thalassemia. The current study indicates that HRI is important for macrophage maturation, although it is expressed at a lower level in macrophages. In HRI deficiency, macrophages do not develop the typical morphology and expressed less CSF-1R protein. Consequently, expression levels of macrophage cell-surface markers F4/80 and CD11b and the core component of the receptor complex for LPS, TLR4, are reduced in Hri–/– compared with Hri+/+ macrophages. This is the first demonstration that HRI protein is expressed and functional in nonerythroid cell types. Further, an impairment of erythrophagocytosis by Hri–/– macrophages was observed under chronic hemolytic anemia induced by PHZ in vivo, providing evidence for the role of HRI in recycling iron from senescent red blood cells. This work demonstrates that HRI deficiency attenuates iron homeostasis in mice, indicating a protective role for HRI in hemolytic anemia of inflammation with exposure to PHZ.
Sijin Liu Rajasekhar N.V.S.Suragani Jane-Jane Chen
Research Center for Eco-Environmental Sciences,Chinese Academy of Sciences,Beijing 100085,China Harv Harvard-MIT Division of Health Sciences and Technology,Massachusetts Institute of Technology,Cambrid
国际会议
北京
英文
1-6
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）