Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation - 09/11/16
, Hirotoshi Unno, MD, PhD b, Hideaki Morita, MD, PhD b, Kyoko Futamura, MD, PhD b, Maiko Emi-Sugie, PhD b, Ken Arae, PhD b, c, Tetsuo Shoda, MD, PhD b, Naoko Okada, PhD b, Arisa Igarashi, PhD b, Eisuke Inoue, PhD d, Hiroshi Kitazawa, MD, PhD e, Susumu Nakae, PhD b, f, g, Hirohisa Saito, MD, PhD b, Kenji Matsumoto, MD, PhD b, ⁎ , Akio Matsuda, PhD b, ⁎ 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.
Le texte complet de cet article est disponible en PDF.Key words : Airway inflammation, asthma, eosinophil, IL-33, papain, platelet
Abbreviations used : AM, BAL, GAPDH, HBSS, HMVEC-L, ILC2, IL1RL1, IM, MDC, MIP, OVA, qPCR, TARC
Plan
| Supported in part by National Institute of Biomedical Innovation grant ID10-43 (to K.M.), grants from the National Center for Child Health and Development #26-9 (to K.M.) and #26-46 (to M.E.-S.), and JSPS KAKENHI grant no. 23591666 (to A.M.). |
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| Disclosure of potential conflict of interest: E. Inoue has consultant arrangements with Tokyo Women's Medical University, is employed by Kitasato University, and has received payment for lectures from Merck Serono. H. Saito is employed by the National Center for Child Health & Development, Japan; has received grants from the Ministry of Health, Labour & Welfare, Japan, and the Japan Society for Promotion of Science; has received payment for lectures from Teijin Pharma, Merck Sharp and Dohme KK, Nippon Boehringer Ingelheim, Shiseido, Ono Pharmaceutical, GlaxoSmithKline KK, Pfizer Japan, Novartis Pharma KK, Kyowa Hakko Kirin, Kyorin Pharmaceutical, Daiichi Sankyo, and AstraZeneca KK; has received payment for development of educational presentations from Toho University School of Medicine; and has received travel support from the Japanese Society of Pediatric Allergy & Clinical Immunology, the Japanese Society of Allergology, and the World Allergy Organization. K. Matsumoto has received grants from the National Institute of Biomedical Innovation (Grant ID10-43) and a grant from the National Center for Child Health and Development (#26-9); is employed by the National Research Institute for Child Health and Development; has received payment for lectures from Merck Sharp and Dohme KK, Ono Pharmaceutical, GlaxoSmithKline, Kyorin Pharmaceutical, Ohtsuka Pharmaceutical, Mitsubishi Tanabe Pharma, AstraZeneca KK, Siemens Healthcare, Abbott Japan, Sumitomo Dainippon Pharma, Maruho, and Teijin Pharma; and has received payment for development of educational presentations from Gifu Pharmaceutical University. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 138 - N° 5
P. 1395 - novembre 2016 Retour au numéro
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