Are they eosinophil extracellular traps?

This perspective critically evaluates the reliance on eosinophil cationic protein (ECP) as a marker for eosinophils in identifying extracellular traps (ETs) in asthma research, as exemplified in the study by Lu et al. While traditionally associated with eosinophilic activity, ECP is also produced by neutrophils, monocytes, and other myeloid cells, undermining its specificity. This limitation risks misattributing ET origin, leading to incorrect pathophysiological interpretations and misdirected therapeutic strategies. In allergic asthma, our findings demonstrate that sensitized neutrophils-rather than eosinophils-form ECP-positive ETs in response to relevant antigens, challenging conclusions that ECP⁺/cit-H3⁺ structures necessarily represent eosinophil extracellular traps (EETs). We advocate for the use of more specific eosinophil markers, such as eosinophil peroxidase (EPO) or major basic protein (MBP), in combination with neutrophil-specific markers, alongside rigorous methodological controls and clinically relevant human models. Accurate identification of ET cellular origins is essential for understanding asthma's heterogeneous inflammatory mechanisms and for guiding the development of targeted, phenotype-specific therapies.