title: Accelerated destruction of erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice.
abstract: OBJECTIVE
  STAT3 is a key modulator of activation and differentiation of macrophages. But it is still unknown if deficiency of STAT3 activates macrophages to destroy erythrocytes by phagocytosis. We generated STAT3 conditional knockout mice by crossing floxed STAT3 mice with Tie2 promoter-driven Cre-recombinase transgenic mice and clarified that Stat3 plays a critical role in the formation and activation of macrophages.
  
  
  METHODS
  Blood cell count, reticulocyte count, serum lactate dehydrogenase, erythropoietin, iron and ferritin concentration, and life span of the erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice were analyzed. To explore the erythropoietic function of the mice, we subjected them to brief hemolytic anemia by injecting them intraperitoneally with phenylhydrazine. The fragility of erythrocytes was examined by scanning electron microscopy and osmotic tolerance test.
  
  
  RESULTS
  The conditional knockout mice had mild normocytic anemia. They also displayed higher lactate dehydrogenase, ferritin and erythropoietin concentration, higher reticulocyte count, and a shorter lifespan of erythrocytes compared with wild-type controls. These data suggest that destruction of erythrocytes and secondary blood formation were accelerated in the STAT3 conditional knockout mice. It didn't appear due to the fragility of erythrocytes. A few of the conditional knockout mice suddenly developed acute severe anemia, high body temperature and massive splenomegaly, and died within 2weeks after the onset of anemia.
  
  
  CONCLUSIONS
  This study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen.
authors.affiliation: Department of Circulatory Physiology, Graduate School of Medicine, Ehime University, Shitsukawa, Toon, Ehime 791-0295, Japan. nobu@m.ehime-u.ac.jp
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohkubo
authors.forename: Yoji
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Aoto
authors.forename: Jun
authors.initials: J
authors.lastname: Yamanouchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Yasukawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Mitsuda
mesh_terms: D000740:Anemia / Q000503:physiopathology; D000818:Animals; D001831:Body Temperature; D004912:Erythrocytes / Q000473:pathology*; D004921:Erythropoietin / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D011401:Promoter Regions, Genetic; D042787:Receptor, TIE-2 / Q000235:genetics*; D017701:Reticulocyte Count; D050796:STAT3 Transcription Factor / Q000235:genetics*; D012720:Severity of Illness Index; D013154:Spleen / Q000166:cytology / Q000473:pathology; D013163:Splenomegaly / Q000209:etiology; D013997:Time Factors
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D004921:Erythropoietin; D005293:Ferritins; D007770:L-Lactate Dehydrogenase; D042787:Receptor, TIE-2
keywords: Anemia; Macrophage; Phagocytosis; Splenomegaly; Stat3