Neutrophil apoptosis is delayed in an equine model of colitis: Implications for the development of systemic inflammatory response syndrome.
Authors: Anderson S L, Singh B
Journal: Equine veterinary journal
Summary
# Neutrophil apoptosis delays in equine colitis and SIRS development Anderson and Singh (2017) investigated whether delayed neutrophil apoptosis—a recognised driver of systemic inflammatory response syndrome in humans—similarly contributes to SIRS development in horses with colitis, using an oligofructose overdose model to induce intestinal inflammation. Neutrophils harvested before and after colitis induction were cultured for 12–24 hours with varying lipopolysaccharide concentrations, then assessed for apoptosis via flow cytometry (Annexin V and propidium iodide staining) alongside measurements of caspase-3, -8 and -9 activity. Post-colitis neutrophils showed significantly delayed apoptosis at both 12 hours (P = 0.004) and 24 hours (P = 0.003), accompanied by reduced activity across all three caspase pathways (caspase-3 P = 0.004; caspase-8 and -9 both P = 0.02), and remarkably, these cells became unresponsive to the apoptosis-delaying effects of LPS. The findings suggest that impaired intrinsic and extrinsic apoptotic signalling in neutrophils—potentially amplified by the neutrophilia occurring during colitis—contributes substantially to SIRS pathogenesis in horses, indicating that therapies targeting neutrophil survival pathways may warrant investigation as adjunctive treatments in severe colitis cases.
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Practical Takeaways
- •Horses with colitis develop delayed neutrophil apoptosis that may perpetuate systemic inflammation; monitoring neutrophil counts and inflammatory markers may help identify and manage SIRS development
- •Understanding that neutrophil lifespan is prolonged in colitis cases suggests that anti-inflammatory interventions targeting apoptosis pathways could be therapeutic targets in managing equine colitis-associated SIRS
- •The concentration-dependent delay in apoptosis implies that neutrophilia itself may exacerbate the inflammatory cascade in colitis, reinforcing the need for aggressive management of the primary colitis lesion
Key Findings
- •Ex vivo neutrophil apoptosis was significantly delayed in neutrophils isolated after colitis induction at both 12-h (P = 0.004) and 24-h (P = 0.003) incubation periods
- •Delayed apoptosis was accompanied by concomitant reductions in caspase-3, -8, and -9 activity, indicating interference with both intrinsic and extrinsic apoptotic pathways
- •Neutrophils isolated post-colitis were refractory to LPS-delayed apoptosis and showed concentration-dependent delay in apoptosis in vitro
- •Delayed neutrophil apoptosis may contribute to the development of equine SIRS and prolonged neutrophilia in colitis cases