Phenotypic and functional characterization of neutrophils from lupus-prone mice (BA4P.223)

Abstract

Abstract Neutrophils constitute a critical component of cellular immunity that eliminate infectious organisms through oxidative burst, phagocytosis and the formation of neutrophil extracellular traps (NETs). Recently it has been reported that neutrophils contribute to autoimmunity through NET formation and interactions with auto-reactive immune cells. Our goal is to characterize phenotypic and functional properties of neutrophils in mouse models of systemic lupus (SLE) to determine if and how neutrophil dysregulation occurs. Using flow cytometry we have measured neutrophil populations in healthy control and diseased SLE mouse models. We found neutrophils are consistently increased in the spleen of MRL-Faslpr, C57BL/6-Faslpr and NZBWF1 lupus mice compared to controls. Further characterization of neutrophil functions including phagocytosis, reactive oxygen production, NET formation, protease activity and histone citrullination indicate increased DNA release, increased citrullination and alterations in serine protease activity in lupus neutrophils. Differences in the results between the NZBWF1 and MRL-Faslpr models suggest the background genetics play a role in neutrophil dysregulation in these two models. Ultimately we hope to understand the cause of altered neutrophil function in mouse models of SLE, whether they contribute to lupus disease progression, and hopefully develop newer targeted therapies for lupus.