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

نویسندگان

  • Joan D Beckman
  • John D Belcher
  • Julie V Vineyard
  • Chunsheng Chen
  • Julia Nguyen
  • M Osita Nwaneri
  • M Gerard O'Sullivan
  • Evin Gulbahce
  • Robert P Hebbel
  • Gregory M Vercellotti
چکیده

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.

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عنوان ژورنال:
  • American journal of physiology. Heart and circulatory physiology

دوره 297 4  شماره 

صفحات  -

تاریخ انتشار 2009