Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation

Tomohiro Takeda, Hirotoshi Unno, Hideaki Morita, Kyoko Futamura, Maiko Emi-Sugie, Ken Arae, Tetsuo Shoda, Naoko Okada, Arisa Igarashi, Eisuke Inoue, Hiroshi Kitazawa, Susumu Nakae, Hirohisa Saito, Kenji Matsumoto, Akio Matsuda

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1395-1403.e6
JournalJournal of Allergy and Clinical Immunology
Issue number5
Publication statusPublished - 01-11-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology


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