Abstract
Carbon monoxide (CO) has anti-inflammatory properties. We previously reported that acute treatments with inhaled CO inhibit vascular inflammation and hypoxia-induced vasoocclusion in sickle cell disease mouse models. Therefore, we hypothesized that chronic CO inhalation would decrease vascular inflammation and organ pathology in a sickle cell disease mouse model. The treatment of sickle cell disease mice with 25 or 250 parts/million inhaled CO for 1 h/day, 3 days/wk for 8-10 wk significantly decreased the total mean white blood cell, neutrophil, and lymphocyte counts in peripheral blood. Eight weeks of 250 parts/million CO treatments reduced staining for myeloid and lymphoid markers in the bone marrow of sickle mice. Bone marrow from treated sickle mice exhibited a significant decrease in colony-forming unit granulocyte-macrophage during colony-forming cell assays. Anti-inflammatory signaling pathways phospho-Akt and phospho-p38 MAPK were markedly increased in CO-treated sickle livers. Importantly, CO-treated sickle mice had a significant reduction in liver parenchymal necrosis, reflecting the anti-inflammatory benefits of CO. We conclude that inhaled CO may be a beneficial anti-inflammatory therapy for sickle cell disease.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Administration, Inhalation
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Anemia, Sickle Cell / blood
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Anemia, Sickle Cell / complications
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Anemia, Sickle Cell / drug therapy*
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Anemia, Sickle Cell / genetics
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Anemia, Sickle Cell / pathology
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Animals
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Anti-Inflammatory Agents / administration & dosage*
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Apoferritins / metabolism
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Carbon Monoxide / administration & dosage*
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Carboxyhemoglobin / metabolism
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Cells, Cultured
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Cytokines / blood
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Dose-Response Relationship, Drug
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Enzyme Activation
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Erythroid Precursor Cells / drug effects
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Female
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Granulocyte-Macrophage Progenitor Cells / drug effects
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Hematopoiesis / drug effects
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Heme Oxygenase-1 / metabolism
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Hemoglobin, Sickle / genetics
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Hemoglobin, Sickle / metabolism
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Hemolysis / drug effects
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Humans
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Leukocyte Count
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Leukocytosis / blood
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Leukocytosis / drug therapy*
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Leukocytosis / genetics
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Leukocytosis / pathology
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Liver / drug effects
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Liver / metabolism
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Liver / pathology
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Lymphocytes / drug effects
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Male
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Necrosis
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Proto-Oncogene Proteins c-akt / metabolism
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Time Factors
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Anti-Inflammatory Agents
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Cytokines
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Hemoglobin, Sickle
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Membrane Proteins
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hemoglobin S-Antilles
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Carbon Monoxide
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Apoferritins
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Carboxyhemoglobin
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Heme Oxygenase-1
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Hmox1 protein, mouse
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Proto-Oncogene Proteins c-akt
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p38 Mitogen-Activated Protein Kinases