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Are they eosinophil extracellular traps?

Pedro Chacón1,2, Adrián López-Postigo1,2, Javier Monteseirín1,2,3

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Eosinophil cationic protein (ECP) is not a specific marker for eosinophil extracellular traps (ETs) in asthma. Neutrophils, not eosinophils, form ECP-positive ETs, necessitating more specific markers for accurate asthma research.

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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.