Are they eosinophil extracellular traps?

Area of Science:

• Immunology
• Respiratory Medicine
• Cell Biology

Background:

• Extracellular traps (ETs) play a role in asthma pathogenesis.
• Eosinophil cationic protein (ECP) is often used as a marker for eosinophil-derived ETs (EETs).
• The specificity of ECP as an eosinophil marker in ET identification is questionable.

Purpose of the Study:

• To critically evaluate the use of ECP as a specific marker for eosinophils in identifying ETs in asthma research.
• To investigate the cellular origin of ECP-positive ETs in allergic asthma.
• To advocate for improved methodologies for identifying ET cellular origin in asthma.

Main Methods:

• Comparative analysis of ECP expression in different myeloid cells.
• Immunofluorescence staining for ECP, citrullinated histone H3 (cit-H3), and cell-specific markers in human asthma models.
• Assessment of ET formation in response to specific antigens in sensitized neutrophils and eosinophils.

Main Results:

• ECP is produced by multiple myeloid cells, including neutrophils, not exclusively eosinophils.
• In allergic asthma models, sensitized neutrophils, not eosinophils, were found to form ECP-positive ETs.
• ECP-positive/cit-H3-positive structures do not exclusively represent eosinophil extracellular traps (EETs).

Conclusions:

• Reliance on ECP alone can lead to misattribution of ET cellular origin in asthma.
• Specific eosinophil markers like eosinophil peroxidase (EPO) or major basic protein (MBP) are needed for accurate identification.
• Precise identification of ET cellular origin is crucial for understanding asthma heterogeneity and developing targeted therapies.