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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 intraperitonea...
Autores principales: | , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Society of Hematology
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575836/ https://www.ncbi.nlm.nih.gov/pubmed/17928531 http://dx.doi.org/10.1182/blood-2007-07-099648 |
Sumario: | 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-1α–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 × 10(6) and 5.4 × 10(6) neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 × 10(6) neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization. |
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