Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses.
Abstract: We report the effects of mouldy hay/straw exposure, inhaled hay dust suspension (HDS) and inhaled lipopolysaccharide (LPS) on bronchoalveolar lavage fluid (BALF) gelatinolytic matrix metalloproteinase (MMP) levels and degree of activation in healthy (n = 6) and heaves- (previously termed chronic obstructive pulmonary disease) affected (n = 6 or 7) horses. Gelatinolytic MMPs in BALF were quantified by zymography, and gelatinases were shown by Western immunoblotting to be MMP-2 and MMP-9. Hay/straw and HDS challenges increased BALF total gelatinolytic activity only in heaves horses, with the majority of gelatinolytic activity comprising pro- and active MMP-9. The 5 h duration hay/straw challenge increased BALF gelatinolytic MMP activity in heaves horses at 5 and 24 h after the start of this challenge, with activity returning to baseline by Day 4. In contrast to hay/straw and HDS challenges, LPS inhalation increased BALF gelatinolytic MMP activity in both groups. For all challenges, absolute BALF neutrophil counts were highly significantly correlated (P0.05). As gelatinolytic MMPs are pro-inflammatory agents, they may contribute to lung dysfunction and tissue destruction in heaves horses exposed to airborne organic stable dusts.
Publication Date: 2002-03-21 PubMed ID: 11902757DOI: 10.2746/042516402776767277Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research assessed how the inhalation of organic dusts and certain bacteria products affects lung enzyme levels in horses with a chronic lung condition. It found that exposure to moldy hay/straw and hay dust suspension increased a type of enzyme called gelatinolytic matrix metalloproteinases, which is known to cause inflammation and potentially lung damage.
Study Overview
- The study focused on the impact of three substances – mouldy hay/straw, hay dust suspension (HDS), and lipopolysaccharide (LPS) – on the levels of certain enzymes in the lung fluid (bronchoalveolar lavage fluid or BALF) in both healthy horses and those suffering from “heaves,” a chronic lung disease similar to human asthma.
- The enzymes being examined were Matrix Metalloproteinases (MMPs), which can degrade components of the connective tissue matrix. The specific MMPs under consideration were MMP-2 and MMP-9.
Methodology and Findings
- The enzyme levels in the BALF were measured using a method known as zymography. Furthermore, they used a Western immunoblotting technique to identify the gelatinases as MMP-2 and MMP-9.
- The study found that exposure to moldy hay/straw and HDS led to an increase in enzyme activity only in horses with heaves. The majority of this activity was composed of the pro- and active form of MMP-9.
- When exposed to a hay/straw challenge for 5 hours, the enzyme activity in the BALF of horses with heaves increased, but returned to normal by the fourth day.
- In contrast, inhaling LPS increased enzyme activity in both healthy horses and those with heaves.
- The study also found a significant correlation between the number of neutrophils (white blood cells) in the BALF and the levels of proMMP-9 and active MMP-9, but not with MMP-2.
Implications
- Gelatinolytic MMPs are agents that can cause inflammation, which implies that they could contribute to lung dysfunction and tissue damage in horses with heaves that are exposed to airborne organic stable dusts.
- This study provides important insights into the potential mechanisms underlying the inflammatory responses in heaves-affected horses, which could inform and guide treatment strategies for this condition.
Cite This Article
APA
Nevalainen M, Raulo SM, Brazil TJ, Pirie RS, Sorsa T, McGorum BC, Maisi P.
(2002).
Inhalation of organic dusts and lipopolysaccharide increases gelatinolytic matrix metalloproteinases (MMPs) in the lungs of heaves horses.
Equine Vet J, 34(2), 150-155.
https://doi.org/10.2746/042516402776767277 Publication
Researcher Affiliations
- Department of Virology and Epidemiology, National Veterinary and Food Research Institute, Faculty of Veterinary Medicine, University of Helsinki, Finland.
MeSH Terms
- Animals
- Bronchoalveolar Lavage Fluid / chemistry
- Bronchoalveolar Lavage Fluid / cytology
- Dust / adverse effects
- Female
- Horse Diseases / enzymology
- Horse Diseases / etiology
- Horse Diseases / pathology
- Horses
- Lipopolysaccharides / adverse effects
- Lung / drug effects
- Lung / enzymology
- Male
- Matrix Metalloproteinase 2 / metabolism
- Matrix Metalloproteinase 9 / metabolism
- Matrix Metalloproteinases / metabolism
- Pulmonary Disease, Chronic Obstructive / enzymology
- Pulmonary Disease, Chronic Obstructive / etiology
- Pulmonary Disease, Chronic Obstructive / pathology
- Pulmonary Disease, Chronic Obstructive / veterinary
Citations
This article has been cited 7 times.- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
- Davis KU, Sheats MK. Differential gene expression and Ingenuity Pathway Analysis of bronchoalveolar lavage cells from horses with mild/moderate neutrophilic or mastocytic inflammation on BAL cytology.. Vet Immunol Immunopathol 2021 Apr;234:110195.
- Barton AK, Shety T, Klier J, Geis S, Einspanier R, Gehlen H. Metalloproteinases and their Inhibitors under the Course of Immunostimulation by CPG-ODN and Specific Antigen Inhalation in Equine Asthma.. Mediators Inflamm 2019;2019:7845623.
- Barton AK, Gehlen H. Pulmonary Remodeling in Equine Asthma: What Do We Know about Mediators of Inflammation in the Horse?. Mediators Inflamm 2016;2016:5693205.
- Barton AK, Shety T, Bondzio A, Einspanier R, Gehlen H. Metalloproteinases and Their Tissue Inhibitors in Comparison between Different Chronic Pneumopathies in the Horse.. Mediators Inflamm 2015;2015:569512.
- Tilton SC, Waters KM, Karin NJ, Webb-Robertson BJ, Zangar RC, Lee KM, Bigelow DJ, Pounds JG, Corley RA. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin.. Toxicol Appl Pharmacol 2013 Mar 1;267(2):137-48.
- Theegarten D, Sachse K, Mentrup B, Fey K, Hotzel H, Anhenn O. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease.. Respir Res 2008 Jan 29;9(1):14.
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