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Expression of pentraxin 3 in equine lungs and neutrophils.

Abstract: Endotoxin-induced diseases cause significant mortality and morbidity in the horse, leading to enormous economic damage to the equine industry. Neutrophils play a critical role in initiating the immune response in the lung. Pattern recognition receptors (PRRs) are programmed to recognize microbial structures unique to pathogens and mount an immune response. Pentraxin 3 (PTX3) is a PRR that is produced at sites of inflammation by many cell types upon stimulation by pro-inflammatory cytokines and agonists, such as endotoxins [also known as lipopolysaccharides (LPS)]. Pentraxin 3 recognizes and binds to many pathogens, activates the complement cascade, and has a role in the clearance of apoptotic and necrotic cells. Recently, PTX3 has been reported to be localized in the specific granules in human and mouse neutrophils, but no reports exist on the localization of PTX3 in neutrophils and the lungs of horses. Therefore, the objective of this study was to localize the PTX3 protein in normal and LPS-exposed neutrophils and in normal equine lungs. Immunohistochemical data showed PTX3 staining in the bronchial epithelial cells and the vascular endothelium of normal lungs. Immunogold electron microscopy localized PTX3 in the nuclei, cytoplasm, and vesicular organelles of alveolar macrophages, endothelial cells, and pulmonary intravascular macrophages. Immunohistochemical staining for PTX3 in isolated horse neutrophils showed an altered staining pattern in neutrophils stimulated with LPS. These data suggest that neutrophils may be a mobile form of PTX3 that is readily shuttled to the site of inflammation, where it can be released to fine tune a host defense response. Les maladies induites par les endotoxines provoquent une mortalité et une morbidité importantes chez le cheval, entraînant d’énormes dommages économiques pour l’industrie équine. Les neutrophiles jouent un rôle essentiel dans le déclenchement de la réponse immunitaire dans les poumons. Les récepteurs de reconnaissance de formes (PRR) sont programmés pour reconnaître les structures microbiennes propres aux agents pathogènes et déclencher une réponse immunitaire. La pentraxine 3 (PTX3) est un PRR qui est produit sur les sites d’inflammation par de nombreux types de cellules lors de la stimulation par des cytokines pro-inflammatoires et des agonistes, tels que les endotoxines [également appelées lipopolysaccharides (LPS)]. La pentraxine 3 reconnaît et se lie à de nombreux agents pathogènes, active la cascade du complément et joue un rôle dans la clairance des cellules apoptotiques et nécrotiques. Récemment, il a été rapporté que PTX3 était localisé dans les granules spécifiques des neutrophiles humains et de souris, mais aucun rapport n’existe sur la localisation de PTX3 dans les neutrophiles et les poumons des chevaux. Par conséquent, l’objectif de cette étude était de localiser la protéine PTX3 dans les neutrophiles normaux et exposés au LPS et dans les poumons équins normaux. Les données immunohistochimiques ont montré une coloration PTX3 dans les cellules épithéliales bronchiques et l’endothélium vasculaire des poumons normaux. La microscopie électronique d’immunomarquage à l’or colloïdal a localisé PTX3 dans les noyaux, le cytoplasme et les organites vésiculaires des macrophages alvéolaires, des cellules endothéliales et des macrophages intravasculaires pulmonaires. La coloration immunohistochimique de PTX3 dans des neutrophiles de cheval isolés a montré un schéma de coloration altéré dans les neutrophiles stimulés avec du LPS. Ces données suggèrent que les neutrophiles peuvent être une forme mobile de PTX3 qui est facilement acheminée vers le site de l’inflammation, où elle peut être libérée pour affiner une réponse de défense de l’hôte.(Traduit par Docteur Serge Messier).
Publication Date: 2023-01-07 PubMed ID: 36606044PubMed Central: PMC9808873
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  • Journal Article

Summary

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The research examines the location and role of pentraxin 3 in equine lungs and neutrophils, focusing on how it responds to endotoxins which cause diseases in horses.

Background

  • Endotoxin-induced diseases pose a significant health threat to horses, leading not only to increased mortality and morbidity but also substantial economic loss to the equine industry.
  • The immune response in the lungs is primarily initiated by neutrophils – immune cells. They have Pattern Recognition Receptors (PRRs) set to identify unique microbial structures attached to pathogens, triggering an immune response.
  • Pentraxin 3 (PTX3) is a type of PRR. It is produced at inflammation sites by multiple cell types, including upon stimulation by pro-inflammatory cytokines and agonists such as endotoxins, or Lipopolysaccharides (LPS).
  • PTX3 recognizes and latches on to many pathogens, activates the complement cascade (a system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells), and plays a role in clearing apoptotic (programmed cell death) and necrotic (cell death due to disease or injury) cells.
  • PTX3 has reportedly been localized in specific granules in human and mouse neutrophils, but its localization in horse neutrophils and lungs was yet unknown.

Objective

  • The purpose of this study was to locate PTX3 protein in normal and LPS-exposed neutrophils, along with normal equine lungs.

Research Findings

  • Immunohistochemical data revealed PTX3 staining in the cells of the bronchial epithelium and vascular endothelium in normal lungs, showing presence there.
  • Immunogold electron microscopy, another staining method, located PTX3 in alveolar macrophages, endothelial cells, and pulmonary intravascular macrophages. These were specifically found in the nuclei, cytoplasm, and vesicular organelles.
  • An altered staining pattern was observed for PTX3 in isolated horse neutrophils that had been stimulated with LPS, suggesting a response to endotoxin.
  • The altered response suggests that neutrophils may represent a movable form of PTX3, transported to inflammation sites. Here, they can be released to fine-tune the host’s immune response.

Conclusion

  • The study adds unique insights into the localization and potential function of PTX3 in horse neutrophils and lungs. This could be key in understanding and potentially improving the equine immune response, particularly in relation to endotoxin-induced diseases.

Cite This Article

APA
Townsend M, Fowler B, Aulakh GK, Singh B. (2023). Expression of pentraxin 3 in equine lungs and neutrophils. Can J Vet Res, 87(1), 9-16.

Publication

ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 87
Issue: 1
Pages: 9-16

Researcher Affiliations

Townsend, Michelle
  • Veterinary Biomedical Sciences (Townsend, Fowler, Singh) and Small Animal Clinical Sciences (Aulakh), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.
Fowler, Brooke
  • Veterinary Biomedical Sciences (Townsend, Fowler, Singh) and Small Animal Clinical Sciences (Aulakh), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.
Aulakh, Gurpreet K
  • Veterinary Biomedical Sciences (Townsend, Fowler, Singh) and Small Animal Clinical Sciences (Aulakh), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.
Singh, Baljit
  • Veterinary Biomedical Sciences (Townsend, Fowler, Singh) and Small Animal Clinical Sciences (Aulakh), Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, Saskatoon, Saskatchewan S7N 5B4.

MeSH Terms

  • Animals
  • C-Reactive Protein / metabolism
  • Cells, Cultured
  • Endothelial Cells / metabolism
  • Horse Diseases
  • Horses
  • Inflammation / metabolism
  • Inflammation / veterinary
  • Lipopolysaccharides / pharmacology
  • Lung / metabolism
  • Neutrophils
  • Serum Amyloid P-Component / metabolism

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