Neutrophils are the most abundant white blood cells and the very first responders to infection, injury, and cancer. They act with remarkable speed, releasing reactive oxygen species, deploying extracellular traps, and reshaping tissues to contain damage and restore balance. But while their role is indispensable, neutrophils remain one of the most challenging immune cells to study.
Over the past decade, intravital microscopy, fluorescent reporter animals, and ex vivo labeling approaches have opened new windows into neutrophil behavior. These methods have revealed how neutrophils swarm toward danger, coordinate with other immune players, and even display dual roles within tumors. Yet, each technique comes with significant trade-offs. Fluorescent reporter models are species-restricted and not easily translatable. Ex vivo labeling risks activating neutrophils before observation, biasing results. Many fluorescent markers also lack cell specificity, leading to potential misinterpretation of data.
One of the major limitations researchers face is the lack of robust, universal tools to track neutrophils across models without altering their native state. Current solutions often compromise accuracy by either over-activating the cells or inadvertently labeling other immune subsets. This gap in reliable tools slows down discoveries and limits our understanding of neutrophil heterogeneity in human health and disease.
Looking forward, novel strategies for neutrophil detection and tracking are emerging. Among them, granule-associated proteins such as lactoferrin are gaining attention as promising candidates for selective targeting. As a key component of neutrophil secondary granules, lactoferrin plays a pivotal role in antimicrobial defense while being tightly linked to neutrophil biology. Leveraging such molecular signatures could provide researchers with more precise and less disruptive ways to visualize and understand these powerful yet elusive cells.
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