Human eosinophils constitutively express a unique serine protease, PRSS33

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Author(s)

    • Toyama Sumika
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development|Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    • Okada Naoko
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development
    • Matsuda Akio
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development
    • Morita Hideaki
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development
    • Saito Hirohisa
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development
    • Nakae Susumu
    • Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, The Institute of Medical Science, The University of Tokyo|Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency
    • Karasuyama Hajime
    • Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University
    • Matsumoto Kenji
    • Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development

Abstract

<p><i>Background:</i> Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis.</p><p><i>Methods:</i> Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system.</p><p><i>Results:</i> Human eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation.</p><p><i>Conclusions:</i> Activated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling.</p>

Journal

  • Allergology International

    Allergology International 66(3), 463-471, 2017

    Japanese Society of Allergology

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