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Murine lung eosinophil activation and chemokine production in allergic airway inflammation

Cellular & Molecular Immunology volume 7, pages 361–374 (2010)Cite this article

Abstract

Eosinophils play important roles in asthma and lung infections. Murine models are widely used for assessing the functional significance and mechanistic basis for eosinophil involvements in these diseases. However, little is known about tissue eosinophils in homeostasis. In addition, little data on eosinophil chemokine production during allergic airway inflammation are available. In this study, the properties and functions of homeostatic and activated eosinophils were compared. Eosinophils from normal tissues expressed costimulation and adhesion molecules B7-1, B7-2 and ICAM-1 for Ag presentation but little major histocompatibility complex (MHC) class II, and were found to be poor stimulators of T-cell proliferation. However, these eosinophils expressed high levels of chemokine mRNA including C10, macrophage inflammatory protein (MIP)-1α, MIP-1γ, MIP-2, eotaxin and monocyte chemoattractant protein-5 (MCP-5), and produced chemokine proteins. Eosinophil intracellular chemokines decreased rapidly with concomitant surface marker downregulation upon in vitro culturing consistent with piecemeal degranulation. Lung eosinophils from mice with induced allergic airway inflammation exhibited increased chemokines mRNA expression and chemokines protein production and upregulated MHC class II and CD11c expression. They were also found to be the predominant producers of the CCR1 ligands CCL6/C10 and CCL9/MIP-1γ in inflamed lungs. Eosinophil production of C10 and MIP-1γ correlated with the marked influx of CD11bhigh lung dendritic cells during allergic airway inflammation and the high expression of CCR1 on these dendritic cells (DCs). The study provided baseline information on tissue eosinophils, documented the upregulation of activation markers and chemokine production in activated eosinophils, and indicated that eosinophils were a key chemokine-producing cell type in allergic lung inflammation.

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Acknowledgements

We thank Mr Bin-Ru Wang, Mr Michael Solga and Ms Linda Mardel for excellent technical assistance. This work was supported in part by the National Institutes of Health Grants HL070065, AI079906 (SJS), HL065344 (CER), AR049449, AR047988 (SMF), HL065228 and K26-RR019709 (JJL), and grants from the Mayo Foundation and American Heart Association (045580Z) (JJL).

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  1. Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, USA

    C Edward Rose Jr

  2. Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Joanne A Lannigan

  3. and Regenerative Medicine and Division of Nephrology, Department of Medicine, Center for Immunity, Inflammation, University of Virginia School of Medicine, Charlottesville, VA, USA

    Paul Kim, Shu Man Fu & Sun-sang J Sung

  4. Division of Pulmonary Medicine, Department of Biochemistry and Molecular Biology, Mayo Clinic Arizona, Scottsdale, AZ, USA

    James J Lee

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Rose, C., Lannigan, J., Kim, P. et al. Murine lung eosinophil activation and chemokine production in allergic airway inflammation. Cell Mol Immunol 7, 361–374 (2010). https://doi.org/10.1038/cmi.2010.31

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