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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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Submitted July 6, 2007
Accepted September 17, 2007
The co-ordinated action of G-CSF and ELR+CXC chemokines in neutrophil mobilisation during acute inflammation
Antje M Wengner, Simon C Pitchford, Rebecca C Furze, and Sara M Rankin*
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom
* Corresponding author; email: s.rankin{at}imperial.ac.uk.
In this study we have identified a unique combinatorial effect of the chemokines KC/MIP-2 and the cytokine G-CSF with respect to the rapid mobilisation of neutrophils from the bone marrow in a model of acute peritonitis. 2h following an intraperitoneal injection of thioglycollate there was a 4.5 fold increase in blood neutrophil numbers which was inhibited by 84% and 72% prior administration of blocking mAbs against either the chemokines KC/ MIP-2 or G-CSF, respectively. An i.p. injection of G-CSF acted remotely to stimulate neutrophil mobilisation, 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 mobilisation by disrupting their SDF-1alpha-mediated retention in the bone marrow. Using an in situ perfusion system of the mouse femoral bone marrow to directly assess mobilisation, KC and G-CSF mobilised 6.8 x 106 and 5.4 x 106 neutrophils respectively, while the infusion of KC and G-CSF together mobilised 19.5 x 106 neutrophils, indicating that these factors act co-operatively with respect to neutrophil mobilisation.

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