In vitro evaluation of the effect of a novel immunosuppressive agent, FTY720, on the function of feline neutrophils.
OBJECTIVE
To use in vitro assays to evaluate the effects of a novel immunosuppressive agent, FTY720, on biological functions (migration, phagocytosis, and production of reactive-oxygen species [ROS]) of feline peripheral neutrophils and determine the cytotoxic effects of FTY720 on feline peripheral neutrophils.


METHODS
Peripheral neutrophils obtained from 8 healthy cats.


METHODS
Peripheral neutrophils were isolated from blood samples obtained from the 8 cats and exposed to the phosphorylated form of FTY720 (FTY720-P). A fluorescence-based in vitro evaluation of migration was performed. Phagocytosis of microbes and production of ROS were evaluated by use of a 2-color flow cytometry system. Samples of whole blood obtained from the cats were incubated with various concentrations of FTY720-P, fluorescein-labeled Staphylococcus aureus, and dihydroethidium. Cytotoxic effects were evaluated by use of propidium iodide staining.


RESULTS
Addition of FTY720-P caused a slight non-significant decrease in phagocytosis and production of ROS by feline peripheral neutrophils. Migration activity of feline peripheral neutrophils was significantly increased by the addition of FTY720-P. Addition of FTY720-P at concentrations considered for clinical use did not increase the death rate of feline peripheral neutrophils.


CONCLUSIONS
FTY720 does not inhibit critical functions of feline peripheral neutrophils in vitro.
Chen
Yi-Je
YJ
Comparative Transplantation Laboratory, Department of Surgical and Radiological Sciences and Center for Companion Animal Health, School of Veterinary Medicine, University of California, Davis, CA 95616-8745, USA.
Kyles
Andrew E
AE
Gregory
Clare R
CR
D000818:Animals; D002415:Cats; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007958:Leukocyte Count; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011409:Propylene Glycols / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D017382:Reactive Oxygen Species; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine