Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome.

This study looked into the occurrence of neutrophil apoptosis, or programmed cell death, in horses developing systemic inflammatory response syndrome (SIRS) as a result of colitis. The findings revealed delayed neutrophil apoptosis, which might contribute to the development of SIRS in horses.

Objective and Methods

• The main aim of this research was to understand the occurrence of ex vivo neutrophil apoptosis in horses and its contribution to the development of SIRS due to colitis.
• A model of colitis was induced in the horses with an overdose of oligofructose. Neutrophils, a type of white blood cell, were isolated before and after the induction of colitis.
• The isolated neutrophils were placed into culture for 12 or 24 hours, with variable amounts of lipopolysaccharide (LPS).
• The occurrence of apoptosis in these neutrophils was then determined using Annexin V and propidium iodide staining. This was quantified using flow cytometry. The activity of caspase-3, -8, and -9 were also measured after a 12-hour incubation period in neutrophil lysates.

Results

• There was a significant delay in the occurrence of ex vivo neutrophil apoptosis in neutrophils that were isolated post-induction of colitis.
• Corresponding reductions in the activity of caspase-3, -8, and -9 were observed. These enzymes are vital for the occurrence of apoptosis.
• These post-colitis neutrophils showed a decreased response to LPS-driven apoptosis delay, which indicates an altered immune response.
• A delay in neutrophil apoptosis was seen with an increase in cell concentration in vitro, indicating a concentration-dependent delay in apoptosis.

Conclusions

• The exact mechanism causing the delay in neutrophil apoptosis was not fully clarified in this study. However, it was noted that interference with the intrinsic and extrinsic apoptotic pathways could be the contributing factor.
• The data indicates that neutrophil apoptosis is delayed in horses that are induced with colitis, potentially contributing to the development of equine SIRS.
• The simultaneous development of neutrophilia, an elevated level of neutrophils, could contribute further to a prolonged neutrophil lifespan due to a concentration-dependent delay in apoptosis.