title: Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation.
abstract: 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.
  
  
  
  We sought to determine the expression of IL-33 protein by platelets and its functional significance in airway inflammation.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Unno
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Morita
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Futamura
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Maiko
authors.initials: M
authors.lastname: Emi-Sugie
authors.affiliation: 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.
authors.forename: Ken
authors.initials: K
authors.lastname: Arae
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shoda
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Okada
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Arisa
authors.initials: A
authors.lastname: Igarashi
authors.affiliation: Clinical Research Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Inoue
authors.affiliation: Division of Allergy, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitazawa
authors.affiliation: 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.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakae
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Saito
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: matsumoto-k@ncchd.go.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. Electronic address: matsuda-a@ncchd.go.jp.
authors.forename: Akio
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D019556:COS Cells; D002452:Cell Count; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D008168:Lung / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010206:Papain; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D010206:Papain
keywords: Airway inflammation; IL-33; asthma; eosinophil; papain; platelet