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Thorax2001; 56(9); 696-702; doi: 10.1136/thorax.56.9.696

Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway.

Abstract: As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation. Methods: Blood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses. Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for different times and apoptosis was determined using the Annexin-V/propidium iodide detection method. Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay. Results: BAL fluid granulocytes from heaves affected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses. Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves affected horses was comparable. The enhanced survival of BAL fluid granulocytes from affected horses was suppressed in the presence of antibodies directed against GM-CSF receptors. Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves affected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies. Conclusions: These data indicate that granulocyte survival is enhanced in the lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma.
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Publication Date: 2001-08-22 PubMed ID: 11514690PubMed Central: PMC1746130DOI: 10.1136/thorax.56.9.696Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the increased survival of lung granulocytes in asthmatic horses, suggesting that granulocyte/macrophage colony stimulating factor (GM-CSF) and its activated pathway, signal transducer and activator of transcription 5 (STAT5), play crucial roles in postponing cell death of these immune cells, thus contributing to inflammation.

Research Objectives and Methodology

  • The research aims to investigate if there is a GM-CSF led increase in lung granulocyte survival in asthma, similar to other inflammatory diseases, leading to the build-up of these immune cells at inflammation sites.
  • The secondary objective was to explore the roles of STAT5, activated by GM-CSF, in allergic inflammation.
  • Asthma was modelled using six healthy and six asthmatic horses. Granulocytes, a type of white blood cell, were obtained from blood and through bronchoalveolar lavage (BAL), a procedure to examine lung tissue.
  • Granulocytes were cultured with or without anti-GM-CSF receptor antibodies for varying lengths of time. The rate of cell death or apoptosis was measured using the Annexin-V/propidium iodide detection method.
  • Further investigation was conducted on nuclear protein extracts from cultured granulocytes to determine STAT5 binding activity using electrophoretic mobility shift assay, a method to study protein-DNA interaction.

Research Findings

  • Granulocytes from BAL fluid obtained from asthmatic horses showed a significant delay in apoptosis when compared to granulocytes from the blood of the same horses, as well as granulocytes from both blood and BAL fluid from healthy horses.
  • No significant difference was observed in apoptosis rates of blood granulocytes from healthy and asthmatic horses. This indicates that the increased granulocyte survival is specific to the lung environment in asthmatic horses.
  • The extended survival of BAL fluid granulocytes from asthmatic horses was suppressed when cultured with anti-GM-CSF receptor antibodies.
  • Higher levels of active STAT5 were found in granulocytes from BAL fluid obtained from asthmatic horses, and these levels decreased significantly when treated with anti-GM-CSF receptor antibodies.

Conclusion

  • The research concludes that in an asthma model, granulocyte survival is enhanced in the lung, implicating a potential role for the GM-CSF activated STAT5 pathway in delaying apoptosis of these lung granulocytes.
  • This unraveled pathway could serve as a target for future therapeutic strategies aimed at reducing lung-specific inflammation in asthmatic conditions. However, further studies are necessary to fully elucidate the mechanistic details and translational relevance of these findings.

Cite This Article

APA
Turlej RK, Fiévez L, Sandersen CF, Dogné S, Kirschvink N, Lekeux P, Bureau F. (2001). Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway. Thorax, 56(9), 696-702. https://doi.org/10.1136/thorax.56.9.696

Publication

Thorax
ISSN: 0040-6376
NlmUniqueID: 0417353
Country: England
Language: English
Volume: 56
Issue: 9
Pages: 696-702

Researcher Affiliations

Turlej, R K
  • Department of Physiology, Faculty of Veterinary Medicine, University of Liège, B-4000 Liège, Belgium.
Fiévez, L
    Sandersen, C F
      Dogné, S
        Kirschvink, N
          Lekeux, P
            Bureau, F

              MeSH Terms

              • Animals
              • Apoptosis / physiology
              • Asthma / pathology
              • Asthma / veterinary
              • Bronchoalveolar Lavage Fluid / cytology
              • Cell Communication
              • Cell Survival / physiology
              • DNA-Binding Proteins / metabolism
              • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
              • Granulocytes / physiology
              • Horse Diseases / metabolism
              • Horse Diseases / pathology
              • Horses
              • Milk Proteins
              • STAT5 Transcription Factor
              • Trans-Activators / metabolism

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