A day (or 5) in a neutrophil's life

In this issue of Blood, Pillay and colleagues apply a novel technique to reliably measure the half-life of circulating neutrophils that does not rely on ex vivo isolation and labeling before reintroduction to the circulation.¹ 

Neutrophils are the most common immune cell in blood and function as professional phagocytes, highly sensitive to the molecular scent of microbes that initiate an innate program of vascular adhesion, transendothelial migration, and killing at the site of infection. This property renders neutrophils notoriously hard to isolate from blood and study in a pristine unactivated state. Hematologic lore indicates that they circulate a mere 8 to 12 hours before exiting the blood stream to either phagocytose foreign invaders or be engulfed themselves by host macrophages.^2-4  By incorporating ²H₂O into the drinking water of humans and mice, Pillay and colleagues effectively labeled neutrophils as the heavy water was incorporated as ²H-labeled adenosine in the DNA of cells produced in the bone marrow. A mathematical model was applied to balance the books between the dynamics of ²H-adenosine in neutrophils and its appearance in serum and urine as degraded cells released it. Estimation of neutrophil half-life is based on the assumption that the rate at which neutrophils enter the blood from bone marrow equals the rate at which they are lost from the circulation, which is reasonable given that the subjects studied also showed no sign of immunologic challenge. The authors arrived at a neutrophil lifetime of 5.4 days in the circulation of humans and .75 days in mice. The latter estimate is on par with reported measures using in vivo labeling techniques in mice, but the duration in humans is approximately 10-fold longer than previously measured using ex vivo labeling techniques in human blood. Such a prolonged lifetime has only been detected for neutrophils called to battle in inflamed tissue, where they are activated by cytokines such as granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, various interleukins, and bacterial lipopolysaccharides that delay apoptosis.^3,5,6  The findings of Pillay et al suggest that the neutrophil's lifespan is not quite as fleeting as once thought and provide impetus to further examine its interactions with other long-lived partners such as dendritic cells, monocytes, and lymphocytes.