Accelerated destruction of erythrocytes in Tie2 promoter-driven STAT3 conditional knockout mice
| Autor: | Jun Yamanouchi, Yoji Suzuki, Noriaki Mitsuda, Nobutaka Ohkubo, Mamoru Aoto, Satoshi Hirakawa, Masaki Yasukawa |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
STAT3 Transcription Factor
Genetically modified mouse Erythrocytes Time Factors Macrophage Phagocytosis Mice Transgenic Severity of Illness Index General Biochemistry Genetics and Molecular Biology Body Temperature Pharmacology Toxicology and Pharmaceutics(all) Mice Reticulocyte Count Conditional gene knockout Animals General Pharmacology Toxicology and Pharmaceutics Promoter Regions Genetic STAT3 Erythropoietin Mice Knockout Stat3 L-Lactate Dehydrogenase biology Biochemistry Genetics and Molecular Biology(all) Macrophages Anemia General Medicine Receptor TIE-2 Angiopoietin receptor Cell biology Ferritins Splenomegaly Microscopy Electron Scanning Cancer research biology.protein Spleen |
| Zdroj: | Life Sciences. 93:380-387 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2013.07.025 |
| Popis: | AimsSTAT3 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.Main methodsBlood 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.Key findingsThe 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.SignificanceThis study provided evidence that STAT3 have a critical role in the destruction of erythrocytes by resident macrophages in the spleen. |
| Databáze: | OpenAIRE |
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