Mouse Models and Tools for the in vivo Study of Neutrophils

Abstract

Neutrophils are the most abundant leukocytes in human blood and critical actors of the immune system. Many neutrophil functions and facets of their activity in vivo were revealed by studying genetically modified mice or by tracking fluorescent neutrophils in animals using imaging approaches. Assessing the roles of neutrophils can be challenging, especially when exact molecular pathways are questioned or disease states are interrogated that alter normal neutrophil homeostasis. This review discusses the main in vivo models for the study of neutrophils, their advantages and limitations. The side-by-side comparison underlines the necessity to carefully choose the right model(s) to answer a given scientific question, and exhibit caveats that need to be taken into account when designing experimental procedures. Collectively, this review suggests that at least two models should be employed to legitimately conclude on neutrophil functions.

Neutrophil-to-hepatocyte communication via LDLR-dependent miR-223–enriched extracellular vesicle transfer ameliorates nonalcoholic steatohepatitis

“…To further determine whether neutrophils contribute to circulating miR-223, we performed neutrophil depletion experiments. Injection of anti-Ly6G or anti-Gr-1 antibodies have been widely used to deplete neutrophils; however, these approaches suffer from limitations of low efficiency or specificity, especially during chronic depletion (28). Indeed, we found that treatment of HFD-fed mice with anti-Gr-1 for two weeks only slightly reduced circulating neutrophils (data not shown).…”

Neutrophils and Influenza: A Thin Line between Helpful and Harmful

“…Studies suggesting a beneficial role for neutrophils in influenza virus infection typically rely on mouse models to monitor the impact of neutrophil depletion before or after infection with influenza viruses. For many years, the monoclonal antibody (mAb) RB6-8C5 was the standard for neutrophil depletion [100]. However, RB6-8C5 binds both Ly6G expressed on neutrophils, and Ly6C present on neutrophils, dendritic cells, and other populations of lymphocytes and monocytes [100].…”

The Secretive Life of Neutrophils Revealed by Intravital Microscopy

“…The not selectivity of specific leukocyte subsets and the high excitation required to detect fluorescent signal caused photodamage and altered leukocyte adhesion and microvascular fluidity (Saetzler et al, 1997). Later studies used genetically modified mice that were generated as tools for in vivo imaging of neutrophil behavior (Stackowicz et al, 2019). In the Lys-EGFP + mice, both neutrophils and monocyte are fluorescently labeled, neutrophils exhibiting high fluorescence, while monocytes are only dim green (Faust et al, 2000).…”