Tomohiro Takeda1, Hirotoshi Unno2, Hideaki Morita2, Kyoko Futamura2, Maiko Emi-Sugie2, Ken Arae3, Tetsuo Shoda2, Naoko Okada2, Arisa Igarashi2, Eisuke Inoue4, Hiroshi Kitazawa5, Susumu Nakae6, Hirohisa Saito2, Kenji Matsumoto7, Akio Matsuda8. 1. Department of Health Sciences, Kansai University of Health Sciences, Osaka, Japan; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: jeni@mbk.ocn.ne.jp. 2. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 3. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Department of Immunology, Faculty of Health Science, Kyorin University, Tokyo, Japan. 4. Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan. 5. Division of Allergy, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan. 6. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan; Laboratory of Systems Biology, Center for Experimental Medicine and Systems Biology, the Institute of Medical Science, the University of Tokyo, Tokyo, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Saitama, Japan. 7. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: matsumoto-k@ncchd.go.jp. 8. Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: matsuda-a@ncchd.go.jp.
Abstract
BACKGROUND: Although platelets play a key role in allergic inflammation in addition to their well-established role in hemostasis, the precise mechanisms of how platelets modulate allergic inflammation are not fully understood. IL-33 is an essential regulator of innate immune responses and allergic inflammation. OBJECTIVE: We sought to determine the expression of IL-33 protein by platelets and its functional significance in airway inflammation. METHODS: IL-33 protein in human platelets, the human megakaryocyte cell line MEG-01, and bone marrow-derived mouse megakaryocytes was detected by using Western blot analysis and fluorescent immunostaining. We examined the functional relevance of IL-33 protein in platelets by comparing platelet-intact and platelet-depleted groups in a murine model of IL-33-dependent airway eosinophilia elicited by intranasal administration of papain. We further compared the additive effect of administration of platelets derived from wild-type versus IL-33-deficient mice on the papain-induced eosinophilia. RESULTS: Platelets and their progenitor cells, megakaryocytes, constitutively expressed IL-33 protein (31 kDa). Papain-induced IL-33-dependent airway eosinophilia in mice was significantly attenuated by platelet depletion. Conversely, concomitant administration of platelets derived from wild-type mice but not IL-33-deficient mice enhanced the papain-induced airway eosinophilia. CONCLUSIONS: Our novel findings suggest that platelets might be important cellular sources of IL-33 protein in vivo and that platelet-derived IL-33 might play a role in airway inflammation. Therefore platelets might become an attractive novel therapeutic target for asthma and probably allergic inflammation.
BACKGROUND: Although platelets play a key role in allergic inflammation in addition to their well-established role in hemostasis, the precise mechanisms of how platelets modulate allergic inflammation are not fully understood. IL-33 is an essential regulator of innate immune responses and allergic inflammation. OBJECTIVE: We sought to determine the expression of IL-33 protein by platelets and its functional significance in airway inflammation. METHODS:IL-33 protein in human platelets, the human megakaryocyte cell line MEG-01, and bone marrow-derived mouse megakaryocytes was detected by using Western blot analysis and fluorescent immunostaining. We examined the functional relevance of IL-33 protein in platelets by comparing platelet-intact and platelet-depleted groups in a murine model of IL-33-dependent airway eosinophilia elicited by intranasal administration of papain. We further compared the additive effect of administration of platelets derived from wild-type versus IL-33-deficient mice on the papain-induced eosinophilia. RESULTS: Platelets and their progenitor cells, megakaryocytes, constitutively expressed IL-33 protein (31 kDa). Papain-induced IL-33-dependent airway eosinophilia in mice was significantly attenuated by platelet depletion. Conversely, concomitant administration of platelets derived from wild-type mice but not IL-33-deficient mice enhanced the papain-induced airway eosinophilia. CONCLUSIONS: Our novel findings suggest that platelets might be important cellular sources of IL-33 protein in vivo and that platelet-derived IL-33 might play a role in airway inflammation. Therefore platelets might become an attractive novel therapeutic target for asthma and probably allergic inflammation.
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