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Equine veterinary journal2005; 37(5); 412-417; doi: 10.2746/042516405774480111

Effect of composition and different fractions of hay dust suspension on inflammation in lungs of heaves-affected horses: MMP-9 and MMP-2 as indicators of tissue destruction.

Abstract: Airway matrix metalloproteinases (MMPs) increase following inhalation of organic dust. The relative contribution of dust components to this elevation is unknown. Objective: To identify components of organic dust responsible for elevated MMP levels in equine airways. Methods: Bronchoalveolar lavage (BALF) from 7 heaves-susceptible horses, collected 6 h following inhalation challenges with saline, 2 different hay dust suspensions (HDS-1 and -2) and soluble and particulate fractions of HDS-1, were analysed for MMP-2 and -9 using SDS-page gelatin zymography. Results: HDS-1 challenge increased BALF proMMP-9 and total MMP-9. HDS-1 fractions, or the particulate fraction with added lipopolysaccharide, increased BALF proMMP-9 and total MMP-9 in combination, but not when inhaled separately. HDS-2 inhalation elevated BALF complex forms, proMMP-9, active MMP-9, total MMP-9 and total MMP-2. Conclusions: The results suggest synergistic action of soluble and particulate organic dust components. The fact that HDS-1 and HDS-2 had different glucan concentrations supports a role for moulds in the activation of MMP-9. Conclusions: Activation and release of MMPs in response to inhaled moulds are involved in the aetiopathogenesis of heaves. Endotoxin contributes to the synergistic action of the dust components, but the overall MMP response to organic dust inhalation in heaves-susceptible horses largely reflects the mould content of the dust. In the future, inhibition of MMP production and release may offer therapeutic means for treatment and prevention of heaves and recommendations for acceptable dust levels can be given.
Publication Date: 2005-09-17 PubMed ID: 16163942DOI: 10.2746/042516405774480111Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research analyzes the effects that different elements of organic dust might have on the increase of matrix metalloproteinases (MMPs) levels—associated with tissue destruction—in the airways of horses prone to a respiratory condition called heaves. The study is particularly concerned with the role of molds.

Research Methodology

  • To discern the connection between organic dust components and MMP elevation, the researchers ran tests on bronchoalveolar lavage (BALF) samples obtained from seven horses susceptible to heaves.
  • The horses were exposed to different inhalation challenge tests: normal saline, two distinct hay dust suspensions (HDS-1 and HDS-2), and soluble and particulate fractions of HDS-1.
  • BALF samples, taken six hours post-inhalation challenge, were evaluated to measure MMP-2 and MMP-9 levels, with SDS-page gelatin zymography technique.

Research Findings

  • HDS-1 challenge caused an increase in BALF proMMP-9 and total MMP-9 levels.
  • The increase in proMMP-9 and total MMP-9 occurred only when the soluble and particulate fractions of HDS-1 were combined or when lipopolysaccharide was added to the particulate fraction, not when inhaled separately.
  • HDS-2 inhalation led to elevated levels of complex forms, proMMP-9, active MMP-9, total MMP-9, and total MMP-2 in BALF.

Conclusions

  • The results show that soluble and particulate organic dust components work together to bring about the increase in MMPs.
  • The varying glucan concentrations in HDS-1 and HDS-2 suggest that molds play a significant part in activating MMP-9 levels.
  • The activations and releases of MMPs due to inhaled molds are seen to be involved in the development and cause of heaves.
  • While the endotoxin does contribute to the action of the dust components, the overall MMP response to organic dust inhalation is largely reflected by the mold content in the dust.
  • The researchers speculate that inhibiting the production and release of MMPs could be an effective strategy in treating and preventing heaves in the future, and provide recommendations for acceptable dust levels.

Cite This Article

APA
Simonen-Jokinen T, Pirie RS, McGorum BC, Maisi P. (2005). Effect of composition and different fractions of hay dust suspension on inflammation in lungs of heaves-affected horses: MMP-9 and MMP-2 as indicators of tissue destruction. Equine Vet J, 37(5), 412-417. https://doi.org/10.2746/042516405774480111

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 37
Issue: 5
Pages: 412-417

Researcher Affiliations

Simonen-Jokinen, T
  • Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Pirie, R S
    McGorum, B C
      Maisi, P

        MeSH Terms

        • Animals
        • Bronchoalveolar Lavage Fluid / chemistry
        • Bronchoalveolar Lavage Fluid / cytology
        • Dose-Response Relationship, Immunologic
        • Dust / immunology
        • Female
        • Horse Diseases / enzymology
        • Horse Diseases / pathology
        • Horses
        • Inhalation Exposure
        • Lung / enzymology
        • Lung / metabolism
        • Male
        • Matrix Metalloproteinase 2 / metabolism
        • Matrix Metalloproteinase 9 / metabolism
        • Pulmonary Disease, Chronic Obstructive / enzymology
        • Pulmonary Disease, Chronic Obstructive / pathology
        • Pulmonary Disease, Chronic Obstructive / veterinary

        Citations

        This article has been cited 6 times.
        1. 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).
          doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
        2. 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.
          doi: 10.1016/j.vetimm.2021.110195pubmed: 33588285google scholar: lookup
        3. 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.
          doi: 10.1155/2019/7845623pubmed: 31316303google scholar: lookup
        4. 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.
          doi: 10.1155/2016/5693205pubmed: 28053371google scholar: lookup
        5. 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.
          doi: 10.1155/2015/569512pubmed: 26770019google scholar: lookup
        6. 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.
          doi: 10.1186/1465-9921-9-14pubmed: 18230187google scholar: lookup