The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation.
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-1alpha-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 10(6) and 5.4 x 10(6) neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 x 10(6) neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization.
Wengner
Antje M
AM
Leukocyte Biology Section, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, United Kingdom.
Pitchford
Simon C
SC
Furze
Rebecca C
RC
Rankin
Sara M
SM
D000208:Acute Disease; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054360:Chemokine CXCL1 / Q000276:immunology* / Q000494:pharmacology; D054377:Chemokine CXCL12 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology* / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010538:Peritonitis / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
C514936:CXCR4 protein, mouse; D054360:Chemokine CXCL1; D054377:Chemokine CXCL12; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor