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Home / Equine Research Bank / Front Vet Sci / Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, ...
Frontiers in veterinary science2017; 4; 159; doi: 10.3389/fvets.2017.00159

Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation.

Abstract: In many equine inflammatory disease states, neutrophil activities, such as adhesion, migration, and reactive oxygen species (ROS) production become dysregulated. Dysregulated neutrophil activation causes tissue damage in horses with asthma, colitis, laminitis, and gastric glandular disease. Non-steroidal anti-inflammatory drugs do not adequately inhibit neutrophil inflammatory functions and can lead to dangerous adverse effects. Therefore, novel therapies that target mechanisms of neutrophil-mediated tissue damage are needed. One potential neutrophil-targeting therapeutic is the PGE1 analog, misoprostol. Misoprostol is a gastroprotectant that induces intracellular formation of the secondary messenger molecule cyclic AMP (cAMP), which has been shown to have anti-inflammatory effects on neutrophils. Misoprostol is currently used in horses to treat NSAID-induced gastrointestinal injury; however, its effects on equine neutrophils have not been determined. We hypothesized that treatment of equine neutrophils with misoprostol would inhibit equine neutrophil adhesion, migration, and ROS production, in vitro. We tested this hypothesis using isolated equine peripheral blood neutrophils collected from 12 healthy adult teaching/research horses of mixed breed and gender. The effect of misoprostol treatment on adhesion, migration, and respiratory burst of equine neutrophils was evaluated via fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced chemiluminescence, respectively. Neutrophils were pretreated with varying concentrations of misoprostol, vehicle, or appropriate functional inhibitory controls prior to stimulation with LTB4, CXCL8, PAF, lipopolysaccharide (LPS) or immune complex (IC). This study revealed that misoprostol pretreatment significantly inhibited LTB4-induced adhesion, LTB4-, CXCL8-, and PAF-induced chemotaxis, and LPS-, IC-, and PMA-induced ROS production in a concentration-dependent manner. This data indicate that misoprostol-targeting of E-prostanoid (EP) receptors potently inhibits equine neutrophil effector functions in vitro. Additional studies are indicated to further elucidate the role of EP receptors in regulating neutrophil function. Overall, our results suggest misoprostol may hold promise as a novel anti-inflammatory therapeutic in the horse.
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Publication Date: 2017-09-28 PubMed ID: 29034248PubMed Central: PMC5626936DOI: 10.3389/fvets.2017.00159Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores the use of misoprostol, a PGE analog, in suppressing activities of equine neutrophils, which are dysregulated in many inflammatory horse diseases causing tissue damage. The research highlights promising results of misoprostol in inhibiting neutrophil adhesion, migration, and reactive oxygen species production, suggesting its potential as an anti-inflammatory treatment for horses.

Objective of the Study

  • The primary goal of the paper is to investigate the effects of misoprostol on equine neutrophils.
  • Specifically, it tests the hypothesis that misoprostol can hinder neutrophil adhesion, migration, and reactive oxygen species (ROS) production, which are generally dysregulated in inflammatory horse diseases and result in tissue damage.

Situation and need for the Study

  • Neutrophils play a significant role in many equine (horse) inflammatory diseases such as asthma, colitis, laminitis, and gastric glandular disease. When their activities become dysregulated, this leads to tissue damage.
  • Non-steroidal anti-inflammatory drugs, though used, aren’t sufficient to suppress neutrophil inflammatory activity and can cause adverse effects.
  • Therefore, there is a need for therapies that target neutrophil-mediated tissue damage directly. Misoprostol, a PGE analog, is posed as such a therapy in this study.

Methodology

  • The researchers used isolated equine peripheral blood neutrophils collected from 12 healthy adult mixed breed and gender horses.
  • The effect of misoprostol on neutrophil adhesion, migration, and respiratory burst was evaluated using fluorescence-based adhesion and chemotaxis assays, and luminol-enhanced chemiluminescence, respectively.
  • The neurons were pretreated with varying concentrations of the drug, a vehicle, or appropriate functional inhibitory controls before being stimulated with certain agents.

Findings

  • The study found that misoprostol pretreatment significantly inhibited adhesion, chemotaxis, and ROS production in equine neutrophils, in a concentration-dependent manner.
  • This suggests that misoprostol’s targeting of E-prostanoid (EP) receptors potently hinders equine neutrophil effector functions.

Implications and Conclusion

  • Additional investigations are encouraged to further understand the role of EP receptors in regulating neutrophil function.
  • The findings suggest that misoprostol may hold potential as a novel anti-inflammatory therapeutic in horses, opening up a new path towards treating equine inflammatory diseases.

Cite This Article

APA
Martin EM, Till RL, Sheats MK, Jones SL. (2017). Misoprostol Inhibits Equine Neutrophil Adhesion, Migration, and Respiratory Burst in an In Vitro Model of Inflammation. Front Vet Sci, 4, 159. https://doi.org/10.3389/fvets.2017.00159

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 4
Pages: 159

Researcher Affiliations

Martin, Emily Medlin
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Till, Rebecca Louise
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
Sheats, Mary Katherine
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • College of Veterinary Medicine, Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.
Jones, Samuel L
  • Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
  • College of Veterinary Medicine, Comparative Medicine Institute, North Carolina State University, Raleigh, NC, United States.

Grant Funding

  • K01 OD015136 / NIH HHS

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