Inhaled carbon monoxide reduces leukocytosis in a murine model of sickle cell disease

1 Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis; 2 Vascular Biology Center, University of Minnesota Medical School, Minneapolis; 3 Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, Saint Paul; and 4 Division of Surgical Pathology, Department of Laboratory Medicine/Pathology, University of Minnesota Medical School, Minneapolis, Minnesota Submitted April 3, 2009 ; accepted in final form July 13, 2009 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. inflammation; heme oxygenase Address for reprint requests and other correspondence: G. M. Vercellotti, Dept. of Medicine, Hematology/Oncology/Transplantation, Rm. D495 Mayo, MMC 480, 420 Delaware St. SE, Minneapolis, MN 55455 (e-mail: verce001{at}umn.edu ).