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Eosinophils Induce Airway Smooth Muscle Cell Proliferation

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Abstract

Asthma is characterized by eosinophilic airway inflammation and remodeling of the airway wall. Features of airway remodeling include increased airway smooth muscle (ASM) mass. However, little is known about the interaction between inflammatory eosinophils and ASM cells. In this study, we investigated the effect of eosinophils on ASM cell proliferation. Eosinophils were isolated from peripheral blood of mild asthmatics and non-asthmatic subjects and co-cultured with human primary ASM cells. ASM proliferation was estimated using Ki-67 expression assay. The expression of extracellular matrix (ECM) mRNA in ASM cells was measured using quantitative real-time PCR. The role of eosinophil derived Cysteinyl Leukotrienes (CysLTs) in enhancing ASM proliferation was estimated by measuring the release of leukotrienes from eosinophils upon their direct contact with ASM cells using ELISA. This role was confirmed either by blocking eosinophil-ASM contact or co-culturing them in the presence of leukotrienes antagonist. ASM cells co-cultured with eosinophils, isolated from asthmatics, but not non-asthmatics, had a significantly higher rate of proliferation compared to controls. This increase in ASM proliferation was independent of their release of ECM proteins but dependent upon eosinophils release of CysLTs. Eosinophil-ASM cell to cell contact was required for CysLTs release. Preventing eosinophil contact with ASM cells using anti-adhesion molecules antibodies, or blocking the activity of eosinophil derived CysLTs using montelukast inhibited ASM proliferation. Our results indicated that eosinophils contribute to airway remodeling during asthma by enhancing ASM cell proliferation and hence increasing ASM mass. Direct contact of eosinophils with ASM cells triggers their release of CysLTs which enhance ASM proliferation. Eosinophils, and their binding to ASM cells, constitute a potential therapeutic target to interfere with the series of biological events leading to airway remodeling and Asthma.

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Acknowledgments

This study was supported by grants from the National Plan for Sciences and Technology, King Saud University, Riyadh, Saudi Arabia (grant number 09-BIO907-02) and Merck Frost (grant number 37561). The Meakins-Christie Laboratories and the McGill University Health Centre-Research Institute (MUHC-RI) are supported in part by a Center grant from Le Fonds de la Recherche en Santé du Québec (FRSQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Asthma Research Chair and Prince Naif Center for Immunology Research, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Rabih Halwani, Alejandro Vazquez-Tello, Mary Angeline Pureza, Ahmed Bahammam, Hamdan Al-Jahdali & Saleh Al-Muhsen

  2. Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada

    Yuki Sumi & Qutayba Hamid

  3. Department of Medicine, Pulmonary Division-ICU, King Saud University for health sciences, Riyadh, Saudi Arabia

    Hamdan Al-Jahdali

  4. Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada

    Abdelillah Soussi-Gounni

  5. University of Sharjah, Sharjah, United Arab Emirates

    Bassam Mahboub

  6. Department of Pediatrics, College of Medicine, King Saud University, P.O.BOX: 2925, 11461, Riyadh, Saudi Arabia

    Saleh Al-Muhsen

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  1. Rabih Halwani
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  2. Alejandro Vazquez-Tello
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Correspondence to Saleh Al-Muhsen.

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Halwani, R., Vazquez-Tello, A., Sumi, Y. et al. Eosinophils Induce Airway Smooth Muscle Cell Proliferation. J Clin Immunol 33, 595–604 (2013). https://doi.org/10.1007/s10875-012-9836-3

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