Inhibition of equine complement activity by polysulfated glycosaminoglycans.

The research investigates the capacity of polysulfated glycosaminoglycans (PSGAGs) to stifle the workings of the equine complement system – part of the immune response. The results demonstrated that PSGAGs could significantly reduce equine complement activity, which might explain the reduction of joint inflammation in horses when PSGAGs are administered.

Background

• The study was driven by an established understanding that the complement system plays a crucial role in inflammation and infection. The researchers therefore sought to explore the ability of polysulfated glycosaminoglycans (PSGAGs) to inhibit it.
• PSGAGs are already identifiable as a potentially beneficial treatment in domain of joint inflammation linked to diarthrodial joint inflammation and septic arthritis in horses.

Methodology

• To evaluate the effect of PSGAGs on the equine complement system, the team performed hemolytic complement testing. This used rabbit erythrocytes (red blood cells) as target cells.
• The study observed the inhibition effect of different concentrations of PSGAGs, ranging from 0.2mg/ml to 0.6mg/ml.

Findings

• The results showed a significant inhibition of equine complement in a dose-related manner.
• However, beyond a concentration of 0.6mg/ml of PSGAGs, additional inhibition did not occur.
• The research further noted that the extent of inhibition didn’t vary across the four horses tested – a strong indication of consistency.
• The study found that PSGAGs seemed to inhibit both the classical and alternate complement pathways with an equal intensity. This could suggest that they have an effect on the complement components that are common to both pathways.

Other Observations and Conclusions

• Interestingly, when heat inactivation was employed for the complement system, all hemolytic activity in the serum from the horses was totally inhibited.
• Overall, the discovery that PSGAGs have an inhibiting effect on the equine complement system potentially offers a major clue as to why they decrease inflammation in joint related issues in horses. Further research is however needed to confirm this finding and better understand the nature and limits of this inhibition.