Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Wengner, Antje M., Pitchford, Simon C., Furze, Rebecca C., Rankin, Sara M.
Formato: Texto
Lenguaje:English
Publicado: American Society of Hematology 2008
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
Descripción
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.