Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses.
Authors: Muko Ryo, Matsuda Hiroshi, Oikawa Masa-Aki, Shin Taekyun, Matsuda Kenshiro, Sato Hiroaki, Sunouchi Tomoya, Tanaka Akane
Journal: Journal of equine veterinary science
Summary
# Editorial Summary: Histidine-Rich Glycoprotein as a Dual Regulator of Equine Neutrophil Function Researchers characterised equine histidine-rich glycoprotein (eHRG) and investigated its multi-faceted effects on neutrophil behaviour, motivated by evidence that HRG levels drop by approximately 50% in human systemic inflammatory response syndrome (SIRS) patients compared with healthy controls—a condition with significant clinical relevance in equine practice. Using isolated equine neutrophils, the team evaluated how eHRG influenced adhesion, migration, phagocytosis, reactive oxygen species (ROS) production, and lysosomal maturation through cell culture assays, chemiluminescence analysis, and microscopic techniques. The findings revealed a nuanced regulatory role: eHRG suppressed several pro-inflammatory functions by reducing LPS-stimulated neutrophil adhesion, inhibiting IL-8-driven chemotaxis, and restraining peak ROS production—yet paradoxically enhanced the innate immune capacity by promoting both phagocytic activity and lysosomal maturation. This "dual regulator" phenotype suggests eHRG may dampen excessive inflammatory cascade amplification whilst maintaining effective pathogen clearance, positioning it as a potential therapeutic target or biomarker for managing SIRS in horses. Practitioners managing cases of severe systemic inflammation, sepsis, or post-operative complications might eventually benefit from monitoring or modulating eHRG levels to calibrate the immune response more precisely.
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Practical Takeaways
- •HRG may serve as a biomarker for SIRS in horses, as plasma levels appear significantly reduced in inflammatory conditions similar to humans
- •eHRG's dual regulatory role suggests potential therapeutic applications in managing excessive or insufficient neutrophil activation during sepsis or inflammatory disease
- •Understanding HRG's effects on neutrophil function could support development of novel treatments for equine SIRS, a serious clinical concern in equine practice
Key Findings
- •Equine HRG reduced neutrophil adhesion when stimulated with LPS
- •eHRG inhibited neutrophil chemotaxis induced by IL-8
- •eHRG restrained peak ROS production from LPS-stimulated neutrophils
- •eHRG promoted phagocytic activity and lysosomal maturation in equine neutrophils