Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.
Abstract: Neutrophil apoptosis and phagocytic clearance have been proposed as key determinants affecting the resolution of airway inflammation. Objective To determine the kinetics of neutrophil priming, recruitment, activation and subsequent clearance in a naturally occurring equine disease model of neutrophilic pulmonary inflammation. Results: A 5 h mouldy hay/straw challenge in hypersensitive horses induced transient pulmonary dysfunction lasting 4 days. At 24 h circulating neutrophils were primed and displayed delayed rates of spontaneous apoptosis in vitro. Neutrophil numbers in the airspaces peaked at 5 h and then fell abruptly, returning to pre-challenge levels by 4 days. Airspace neutrophils demonstrated increased respiratory burst activity compared with circulating cells and equine neutrophil elastase 2A concentrations increased in parallel with neutrophil numbers indicating in vivo priming and degranulation. The number of apoptotic neutrophils and proportion of alveolar macrophages containing phagocytosed apoptotic neutrophils increased significantly at 24 h and 4 days post-challenge corresponding to the period of most rapid neutrophil clearance. Conclusions: This is the first demonstration of spontaneous neutrophil apoptosis and phagocytic removal in a natural disease model of airway inflammation and provides critical kinetic data to support the hypothesis that this clearance pathway plays a central role in the resolution of neutrophilic inflammation.
Publication Date: 2005-07-13 PubMed ID: 16008670DOI: 10.1111/j.1365-2222.2005.02231.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research explores the progress of neutrophil recruitment and clearance in a naturally occurring equine disease model of pulmonary inflammation, suggesting that apoptosis of neutrophils and their phagocytic removal play a crucial role in resolving airway inflammation.
Objective of the Research
- This study was conducted to examine the progression of neutrophil priming, recruitment, activation, and subsequent clearance in a natural equine disease model of neutrophilic pulmonary inflammation. The term “neutrophilic” refers to an increase in neutrophils, a type of white blood cell, in response to infection or inflammation.
Research Methodology
- Pulmonary inflammation was induced in hypersensitive horses through a 5-hour moldy hay/straw challenge. This triggered temporary lung dysfunction, which lasted 4 days.
- At the 24-hour mark, researchers observed priming of circulating neutrophils, making them more capable of responding to pathogens, as well as a delay in their spontenous apoptosis (natural cell death).
- The researchers closely tracked the numbers of neutrophils in the airspaces, the changes in their activities, and their concentrations to evaluate the in-vivo priming and degranulation processes. The number of neutrophils peaked at 5 hours after the challenge and then rapidly decreased, returning to pre-challenge levels by the end of 4 days.
Findings of the Study
- The study revealed an increase in the respiratory burst activity of airspace neutrophils compared to circulating cells, suggesting in-vivo priming and degranulation. The concentration of equine neutrophil elastase 2A, an enzyme associated with neutrophils, also paralleled the number of neutrophils, indicating further priming and degranulation.
- The researchers also noted a significant increase in the number of apoptotic neutrophils, as well as the proportion of alveolar macrophages containing phagocytosed apoptotic neutrophils, 24 hours and 4 days post-challenge.
- This corresponds to the period of the most rapid neutrophil clearance. These findings together lend support to the hypothesis that the apoptosis of neutrophils and their subsequent phagocytic removal significantly contribute to the resolution of neutrophilic inflammation.
Conclusion of the Research
- The study concludes by highlighting its contribution as the first to demonstrate spontaneous neutrophil apoptosis and phagocytic removal in a natural disease model of airway inflammation. The researchers also emphasize that their work provides critical kinetic data that bolsters the hypothesis of neutrophil clearance playing a central role in resolving neutrophilic inflammation.
Cite This Article
APA
Brazil TJ, Dagleish MP, McGorum BC, Dixon PM, Haslett C, Chilvers ER.
(2005).
Kinetics of pulmonary neutrophil recruitment and clearance in a natural and spontaneously resolving model of airway inflammation.
Clin Exp Allergy, 35(7), 854-865.
https://doi.org/10.1111/j.1365-2222.2005.02231.x Publication
Researcher Affiliations
- Wellcome Trust Centre for Research in Comparative Respiratory Medicine, Easter Bush Veterinary Centre, University of Edinburgh, Roslin, Midlothian, Scotland, UK.
MeSH Terms
- Allergens / immunology
- Animals
- Apoptosis / immunology
- Bronchiolitis / immunology
- Bronchoalveolar Lavage Fluid / cytology
- Bronchoalveolar Lavage Fluid / immunology
- Disease Models, Animal
- Horses
- Immunohistochemistry
- Kinetics
- Leukocyte Count
- Leukocyte Elastase / analysis
- Lung / immunology
- Macrophages / immunology
- Microscopic Angioscopy / methods
- Neutrophils / immunology
- Phagocytosis / immunology
- Respiratory Hypersensitivity / immunology
Grant Funding
- Wellcome Trust
Citations
This article has been cited 19 times.- Xiang Z, Guan X, Ma Z, Shi Q, Panteleev M, Ataullakhanov FI. Bioactive fibrous scaffolds with programmable release of polypeptides regulate inflammation and extracellular matrix remodeling. Regen Biomater 2023;10:rbad010.
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- Bright LA, Dittmar W, Nanduri B, McCarthy FM, Mujahid N, Costa LR, Burgess SC, Swiderski CE. Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation. Vet Med (Auckl) 2019;10:43-63.
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- Conley HE, Davis KU, Adler KB, Lavoie JP, Sheats MK. MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma. Respir Res 2025 Apr 2;26(1):126.
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