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

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• 作者：Tomohiro Takeda ; PhD^a ; ^b ; ^{jeni@mbk.ocn.ne.jp" class="auth_mail" title="E-mail the corresponding author} ; 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 ; ^{matsumoto-k@ncchd.go.jp" class="auth_mail" title="E-mail the corresponding author} ; Akio Matsuda ; PhD^b ; ^{matsuda-a@ncchd.go.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Airway inflammation ; asthma ; eosinophil ; IL-33 ; papain ; platelet
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：138
• 期：5
• 页码：1395-1403.e6
• 全文大小：2403 K

文摘

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.