Carbon Monoxide Decreases Leukocytosis in Murine Sickle Cell Disease Models Via Decreased Granulopoiesis
| Autor: | Joan D. Beckman, Chunsheng Chen, Julie V. Vineyard, John D. Belcher, Michael O Nwaneri, Paul C. Marker, Gregory M. Vercellotti, Julia Ngyuen |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Sickle cell trait medicine.diagnostic_test Bilirubin business.industry Immunology Cell Biology Hematology Hematocrit medicine.disease Biochemistry Granulopoiesis Sickle cell anemia Acute chest syndrome chemistry.chemical_compound Endocrinology medicine.anatomical_structure chemistry Internal medicine White blood cell medicine Leukocytosis medicine.symptom business |
| Zdroj: | Blood. 112:1433-1433 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.v112.11.1433.1433 |
| Popis: | Elevated white blood cell counts (WBC) in sickle cell disease (SCD) are risk factors for morbid vaso-occlusive events including acute chest syndrome and stroke. The mechanisms of leukocytosis in SCD include increased inflammation, oxidative stress, increased hematopoiesis, and hyposplenism. Heme oxygenase-1 (HO-1) plays critical roles in metabolizing the excess heme generated during hemolysis and in modulating vaso-occlusion in murine models of sickle cell disease (SCD). The products of HO-1 activity, carbon monoxide (CO), Fe2+/ferritin, and biliverdin/bilirubin have demonstrable anti-oxidant and anti-inflammatory effects. We have previously demonstrated that inhaled CO treatments decrease white blood cell counts (WBC), as well as liver redox-active iron and heme content in heterozygous BERK mice, a mouse model for sickle cell trait. To dissect the mechanism of this decrease in leukocytosis, we hypothesize that prolonged treatment with inhaled CO significantly decreases granulopoiesis in SCD mice. For this study, we exposed S+S-Antilles mice to 250 ppm inhaled CO for 1h 3X/week for 8–10 weeks. Upon completion of the treatment period animals were euthanized, blood was removed by cardiac puncture, and bone marrow and organs were harvested for analysis. Treatment for 10 weeks with 250 ppm CO significantly decreased total WBC (19.19±1.29 × 1000/ul (untreated) to 12.8±1.30 × 1000/ul (CO treated), p |
| Databáze: | OpenAIRE |
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