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Blood, 1 January 2008, Vol. 111, No. 1, pp. 42-49.
Prepublished online as a Blood First Edition Paper on October 10, 2007; DOI 10.1182/blood-2007-07-099648.
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CHEMOKINES, CYTOKINES, AND INTERLEUKINS
The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation
Antje M. Wengner1,
Simon C. Pitchford1,
Rebecca C. Furze1, and
Sara M. Rankin1
1 Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom
In this study, we have identified a unique combinatorial effect of the chemokines KC/MIP-2 and the cytokine granulocyte colony-stimulating factor (G-CSF) with respect to the rapid mobilization of neutrophils from the bone marrow in a model of acute peritonitis. At 2 hours following an intraperitoneal injection of thioglycollate, there was a 4.5-fold increase in blood neutrophil numbers, which was inhibited 84% and 72% by prior administration of blocking mAbs against either the chemokines KC/MIP-2 or G-CSF, respectively. An intraperitoneal injection of G-CSF acted remotely to stimulate neutrophil mobilization, but did not elicit recruitment into the peritoneum. Further, in vitro G-CSF was neither chemotactic nor chemokinetic for murine neutrophils, and had no priming effect on chemotaxis stimulated by chemokines. Here, we show that, in vitro and in vivo, G-CSF induces neutrophil mobilization by disrupting their SDF-1 –mediated retention in the bone marrow. Using an in situ perfusion system of the mouse femoral bone marrow to directly assess mobilization, KC and G-CSF mobilized 6.8 x 106 and 5.4 x 106 neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 x 106 neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization.
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