Eosinophil ribonucleases and their cutaneous lesion-forming activity

Area of Science:

• Immunology
• Dermatology
• Pathophysiology

Background:

• Eosinophil granule proteins are present in skin lesions of various human diseases.
• The precise role of these proteins in disease pathophysiology remains unclear.

Purpose of the Study:

• To investigate the effects of key eosinophil granule proteins on skin integrity and inflammation.
• To determine the critical factors driving lesion formation by these proteins.

Main Methods:

• Intradermal injection of purified eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein-1 (MBP1) into guinea pig and rabbit skin.
• Histological analysis and assessment of lesion development, cellular infiltration, and protein localization.
• Comparison of induced lesions with human hypereosinophilic syndrome skin lesions.

Main Results:

• ECP and EDN induced distinct ulcerated and crusted skin lesions, respectively, with significant cellular infiltration.
• EPO and MBP1 caused milder, transient skin reactions (induration, erythema) with less infiltration.
• ECP and EDN localized intracellularly and were critical for lesion formation, with RNase activity playing a key role.
• Human hypereosinophilic syndrome lesions showed similar ECP and EDN deposition.

Conclusions:

• ECP and EDN directly disrupt skin integrity and promote inflammation.
• The findings provide a mechanistic explanation for skin manifestations in eosinophil-associated diseases.
• Cellular localization and RNase activity are crucial for ECP and EDN-induced skin pathology.