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This Article Full Text Full Text (PDF) All Versions of this Article: fj.08-109876v1 22/9/3111    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Furze, R. C. Articles by Rankin, S. M. PubMed PubMed Citation Articles by Furze, R. C. Articles by Rankin, S. M.

The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse

Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK

¹Correspondence: Leukocyte Biology Section, Sir Alexander Fleming Building, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, UK SW7 2AZ. E-mail: s.rankin{at}imperial.ac.uk

In humans, 10¹¹ neutrophils are released from the bone marrow per day, and these cells have a half-life in the blood of only 6.5 h. Although it is generally believed that neutrophils are cleared from the circulation via the liver and spleen, in this study using ¹¹¹In-labeled senescent neutrophils, we show that in mice, 32% of neutrophils are cleared from the circulation via the bone marrow. We have previously shown that senescent neutrophils home to the bone marrow in a CXCR4-dependent manner, and we show here that pretreatment of neutrophils with pertussis toxin significantly inhibits neutrophil clearance via the bone marrow (75%), consistent with a role for chemokines in this process. By labeling senescent neutrophils with inert fluorescent microspheres, we have tracked their fate and shown that in vivo, they are ultimately phagocytosed by bone marrow stromal macrophages. Finally, we show that under noninflammatory conditions, circulating levels of neutrophils are regulated by granulocyte-colony stimulating factor (G-CSF), but not interleukin-17. Interestingly, we report that the uptake of apoptotic neutrophils by bone marrow macrophages stimulates their production of G-CSF in vitro. Taken together, these data provide evidence that the bone marrow represents a major site of neutrophil clearance in mice.—Furze, R. C., Rankin, S. M. The role of the bone marrow in neutrophil clearance under homeostatic conditions in the mouse.

Key Words: macrophage • apoptosis • chemokine