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Blood, 29 July 2010, Vol. 116, No. 4, pp. 511-512.

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InsideBlood

PHAGOCYTES & GRANULOCYTES

Comment on Pillay et al, page 625

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

Scott I. Simon, and Min-Ho Kim

UNIVERSITY OF CALIFORNIA DAVIS

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.24 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.

Footnotes

Conflict-of-interest disclosure: The authors declare no competing financial interests. {blacksquare}

REFERENCES

  1. Pillay J, den Braber I, Vrisekoop N, et al. In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days. Blood. 2010;116(4):625–627.[Abstract/Free Full Text]

  2. Basu S, Hodgson G, Katz M, Dunn AR. Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation. Blood. 2002;100(3):854–861.[Abstract/Free Full Text]

  3. Cheretakis C, Leung R, Sun CX, Dror Y, Glogauer M. Timing of neutrophil tissue repopulation predicts restoration of innate immune protection in a murine bone marrow transplantation model. Blood. 2006;108(8):2821–2826.[Abstract/Free Full Text]

  4. Dancey JT, Deubelbeiss KA, Harker LA, Finch CA. Neutrophil kinetics in man. J Clin Invest. 1976;58(3):705–715.[Medline] [Order article via Infotrieve]

  5. Colotta F, Re F, Polentarutti N, Sozzani S, Mantovani A. Modulation of granulocyte survival and programmed cell death by cytokines and bacterial products. Blood. 1992;80(8):2012–2020.[Abstract/Free Full Text]

  6. Kim MH, Liu W, Borjesson DL, et al. Dynamics of neutrophil infiltration during cutaneous wound healing and infection using fluorescence imaging. J Invest Dermatol. 2008;128(7):1812–1820.[CrossRef][Medline] [Order article via Infotrieve]


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Related Article in Blood Online:

In vivo labeling with 2H2O reveals a human neutrophil lifespan of 5.4 days
Janesh Pillay, Ineke den Braber, Nienke Vrisekoop, Lydia M. Kwast, Rob J. de Boer, José A. M. Borghans, Kiki Tesselaar, and Leo Koenderman
Blood 2010 116: 625-627. [Abstract] [Full Text] [PDF]




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