Characterization of arginase expression by equine neutrophils.
Abstract: Neutrophils are the predominant cells recruited in the airways of horses suffering from heaves. These cells have been shown to express arginase in some species. The metabolism of l-arginine is thought to be involved in chronic inflammation, and airway obstruction and remodeling. The aim of this study was to assess the expression, regulation, activity, and functional role of arginase isoforms in equine neutrophils. Arginase I, arginase II, ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) expression were assessed in resting and stimulated (IL-4, LPS/fMLP, PMA; 5 and 18 h) blood neutrophils using quantitative PCR. Arginase expression was also studied by Western blot and enzyme activity assay. The effect of nor-NOHA (1mM), a specific arginase inhibitor, was assessed on arginase activity in vitro and ex vivo on neutrophil's inflammatory gene expression and viability. Results showed that equine neutrophils constitutively express arginase isoform 2, ODC and OAT. Neutrophil ex vivo stimulation did not induce arginase I or influence arginase II mRNA expression. Ex vivo inhibition of arginase activity by nor-NOHA had no effect on neutrophils inflammatory gene expression induced by LPS/fMLP (5h) but significantly reversed the cell loss observed after this stimulation.
Copyright © 2013 Elsevier B.V. All rights reserved.
Publication Date: 2013-12-30 PubMed ID: 24424274DOI: 10.1016/j.vetimm.2013.12.007Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the expression and function of arginase, an enzyme involved in inflammation, in the immune cells of horses with a respiratory condition known as ‘heaves’. The study uses various experiments to demonstrate that these cells inherently express specific versions of the enzyme and that inhibiting the enzyme’s activity can influence the survival of these cells under inflammatory conditions.
Neutrophils and Arginase
- The term ‘neutrophils’ refers to specific white blood cells that play a central role in the body’s immune response, particularly to bacterial infections. For horses suffering from ‘heaves’ (an equine respiratory condition similar to human asthma), neutrophils are the main cells involved in the inflammation response within the airways.
- The researchers were particularly interested in arginase, an enzyme involved in the body’s processing of the amino acid l-arginine. Previous research proposed that this process could be involved in the chronic inflammation seen in heaves, potentially influencing airway obstruction and architectural changes.
Key Findings
- The primary aim of the experiments was to characterize the behavior of arginase in equine neutrophils – this included understanding its regulation, activity, and specific role, as well as identifying the different types (isoforms) of the enzyme expressed by these cells.
- In particular, the researchers found that equine neutrophils express arginase isoform 2, in addition to other related enzymes (ornithine decarboxylase, ODC; and ornithine aminotransferase, OAT). This was a consistent feature of the cells, regardless of whether they were in a standard ‘resting’ state or had been stimulated by various molecules (including IL-4, LPS/fMLP, PMA) that usually elicit a cell response.
- Interestingly, stimulating the neutrophils did not lead to increased expression of arginase 1. This suggests that other control mechanisms might be influencing the cell’s enzyme production under different conditions.
- The final part of the research involved testing the effects of an arginase inhibitor, nor-NOHA. The aim was to see if blocking the enzyme’s activity could impact the neutrophils’ inflammatory reactions, or their viability (ability to survive and function). Here, the team discovered that while nor-NOHA didn’t impact the cells’ inflammatory reactions, it significantly prevented cell death after stimulation.
Implications and Conclusions
- The overall results of the study confirm the consistent expression of arginase in equine neutrophils, while also suggesting that the enzyme might have a role in maintaining cell survival during inflamed conditions. This could be a crucial insight for treating conditions such as ‘heaves’ where inflammation and cell death are primary disease manifestations.
- However, this is a preliminary research and deeper investigations are required to fully understand the complex interactions between arginase, l-arginine metabolism, and the inflammatory process involved in airway diseases in horses.
Cite This Article
APA
Lavoie-Lamoureux A, Martin JG, Lavoie JP.
(2013).
Characterization of arginase expression by equine neutrophils.
Vet Immunol Immunopathol, 157(3-4), 206-213.
https://doi.org/10.1016/j.vetimm.2013.12.007 Publication
Researcher Affiliations
- Faculté de médicine vétérinaire, Dép. de sciences cliniques, Université de Montréal, St-Hyacinthe, Canada.
- Meakins-Christie Laboratories, McGill University, Montreal, Canada.
- Faculté de médicine vétérinaire, Dép. de sciences cliniques, Université de Montréal, St-Hyacinthe, Canada. Electronic address: Jean-pierre.lavoie@umontreal.ca.
MeSH Terms
- Animals
- Arginase / antagonists & inhibitors
- Arginase / genetics
- Arginase / physiology
- Arginine / analogs & derivatives
- Arginine / pharmacology
- Cells, Cultured
- Female
- Horses / immunology
- Humans
- Lipopolysaccharides / pharmacology
- Neutrophils / enzymology
Citations
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