The role of neutrophils and G-CSF in DNFB-induced contact hypersensitivity in mice.
Neutrophils are thought to play an important role during contact hypersensitivity (CHS) in mice, a notion which is supported by studies in which neutrophils are depleted by monoclonal antibodies (mAb). Here, we show that administration of the commonly used anti-mouse Ly6G/C mAb (clone RB6.8C5) leads to depletion of not only neutrophils but also a population of monocytes and macrophages. In contrast, depletion using a Ly6G-specific mAb (clone 1A8) only leads to depletion of neutrophils. We demonstrate that the anti-Ly6G/C mAb suppresses the inflammatory response to a higher extent than the anti-Ly6G mAb suggesting that the impact of neutrophil-depletion in the CHS model may have been overstated when based on protocols using the anti-Ly6G/C mAb. Still, the role of neutrophils in CHS is substantiated as we demonstrate that G-CSF is an important regulator of neutrophil mobilization and effector function in CHS. Indeed, G-CSF was detectable both in the inflamed tissue and in serum during the immune response and we show that blocking G-CSF results in a reduced number of neutrophils in the blood and an attenuation of the ear-swelling response in the tissue. In conclusion, this study supports that neutrophils are important drivers of inflammation in the DNFB-induced CHS model and shows that G-CSF is a significant factor in mobilizing neutrophils during the response.
Department of Immunopharmacology, Novo Nordisk A/S Novo Nordisk Park, Måløv, Denmark ; Department of Veterinary Disease Biology, Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen Stigbøjlen 7, Frederiksberg C, Denmark.
Anne Deen
AD
Christensen
Department of Veterinary Disease Biology, Section for Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen Stigbøjlen 7, Frederiksberg C, Denmark.
Søren
S
Skov
Department of Immunopharmacology, Novo Nordisk A/S Novo Nordisk Park, Måløv, Denmark.
Claus
C
Haase
Contact hypersensitivity; and neutrophils; neutrophil mobilization G-CSF