Volume 6 Supplement 3

Fifth Annual Research Conference: Innovation from Cell to Society

Open Access

Immunoregulatory role of secretory leukocyte protease inhibitor in allergic asthma

  • Rafael Marino1Email author,
  • Thusanth Thuraisingam2,
  • Pierre Camateros1,
  • Yong Zhong Xu1,
  • Jennifer Henri3,
  • Jingxuan Yang4,
  • Guoan He5,
  • Aihao Ding5 and
  • Danuta Radzioch6
Allergy, Asthma & Clinical Immunology20106(Suppl 3):P24

https://doi.org/10.1186/1710-1492-6-S3-P24

Published: 26 November 2010

Background

Asthma is a complex and multi-factorial inflammatory disease [1]. It is one of the most common chronic diseases among children and adolescents [2]. Secretory leukocyte protease inhibitor (SLPI) has shown higher levels in asthmatic patients and its function as an anti-inflammatory protein has been documented in respiratory diseases [3, 4]. However, its role in the immunomodulation of the response during allergic asthma has not yet been fully elucidated. The aim of this study was to evaluate the role of SLPI in the development of phenotypes associated with allergic asthma, and the effect of resiquimod treatment on the SLPI and the possible mechanisms of action involved in the disease.

Materials and methods

The importance of SLPI was assessed by evaluating airway resistance and inflammatory parameters in SLPI transgenic and knock-out mice using an ovalbumin (OVA)-induced model of acute allergic asthma and treatment with resiquimod.

Results

Allergic SLPI transgenic mice showed a significant decrease in airway resistance compared to wild-type mice (6.3 ± 1.1 vs. 8.0 ± 2.1 cm H20 × s/ml, p < 0.001), the same effect was observed with inflammatory cell infiltration, eosinophil percentage (24 ± 1.1% vs. 29 ± 2.3%, p < 0.001), goblet cells (6 ± 1.4 vs. 36 ± 4.0%, p < 0.001) in the lungs and IgE levels (2014.1 ± 309.2 vs. 4173.2 ± 685.6 ng/ml, p < 0.001) in plasma. Allergic SLPI knock-out mice displayed significantly higher values compared to wild-type mice. They include lung resistance (8.6 ± 2.7 vs. 6.6 ± 0.5 cm H20*s/ml, p < 0.001), inflammatory cell influx, eosinophils (36.0 ± 2.7 vs. 29.0 ± 1.5%, p < 0.001), goblet cells (40 ± 4.1 vs. 30 ± 1.4%, p < 0.001), cytokine levels in the lungs (p < 0.05) and plasma IgE levels (3598 ± 204.7 vs. 2763 ± 220.3 ng/ml, p < 0.001). Expression of SLPI decreased inflammation in the lungs, plasma IgE levels, and lung resistance, whereas the ablation of SLPI has the opposite effect. Treatment with resiquimod improved airway resistance and inflammation of the lungs in SLPI knock-out and wild type, demonstrating that its effect is independent of the expression of SLPI.

Conclusions

SLPI plays an immunoregulatory role in the respiratory tract by reducing the inflammatory process and by improving lung physiology in a murine model of acute allergic asthma.

Declarations

Acknowledgements

R. Marino and P. Camateros are both supported by a CIHR Doctoral Award. We acknowledge the histology expert assistance of Dr. Marie-Christine Guiot.

Authors’ Affiliations

(1)
Department of Medicine, Montreal General Hospital, Research Institute, McGill University
(2)
Faculty of Medicine, University of Montreal
(3)
Montreal General Hospital, Research Institute, McGill University
(4)
Institute of Cell Biology, Swiss Federal Institute of Technology Zürich
(5)
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York
(6)
Faculty of Medicine, Department of Medicine and Department of Human Genetics, McGill University

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Copyright

© Marino et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

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