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Am J Physiol Heart Circ Physiol 297: H1243-H1253, 2009. First published July 17, 2009; doi:10.1152/ajpheart.00327.2009
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Inhaled carbon monoxide reduces leukocytosis in a murine model of sickle cell disease

Joan D. Beckman,1,2 John D. Belcher,1,2 Julie V. Vineyard,1,2 Chunsheng Chen,1,2 Julia Nguyen,1,2 M. Osita Nwaneri,1,2 M. Gerard O'Sullivan,3 Evin Gulbahce,4 Robert P. Hebbel,1,2 and Gregory M. Vercellotti1,2

1Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota Medical School, Minneapolis; 2Vascular Biology Center, University of Minnesota Medical School, Minneapolis; 3Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, Saint Paul; and 4Division 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).







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