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

被引:42
|
作者
Takeda, Tomohiro [1 ,2 ]
Unno, Hirotoshi [2 ]
Morita, Hideaki [2 ]
Futamura, Kyoko [2 ]
Emi-Sugie, Maiko [2 ]
Arae, Ken [2 ,3 ]
Shoda, Tetsuo [2 ]
Okada, Naoko [2 ]
Igarashi, Arisa [2 ]
Inoue, Eisuke [4 ]
Kitazawa, Hiroshi [5 ]
Nakae, Susumu [2 ,6 ,7 ]
Saito, Hirohisa [2 ]
Matsumoto, Kenji [2 ]
Matsuda, Akio [2 ]
机构
[1] Kansai Univ Hlth Sci, Dept Hlth Sci, 2-11-1 Wakaba, Kumatori, Osaka 5900482, Japan
[2] Natl Res Inst Child Hlth & Dev, Dept Allergy & Clin Immunol, Tokyo, Japan
[3] Kyorin Univ, Fac Hlth Sci, Dept Immunol, Tokyo, Japan
[4] Natl Ctr Child Hlth & Dev, Clin Res Ctr, Tokyo, Japan
[5] Natl Ctr Child Hlth & Dev, Dept Med Subspecialties, Div Allergy, Tokyo, Japan
[6] Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol, Lab Syst Biol, Tokyo, Japan
[7] Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol PRESTO, Saitama, Japan
关键词
Airway inflammation; asthma; eosinophil; IL-33; papain; platelet; INNATE LYMPHOID-CELLS; IL-1-LIKE CYTOKINE IL-33; NATURAL HELPER-CELLS; ALLERGIC INFLAMMATION; IN-VIVO; LUNG INFLAMMATION; TYPE-2; IMMUNITY; ST2; RECEPTOR; MAST-CELLS; ASTHMA;
D O I
10.1016/j.jaci.2016.01.032
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 IL33- deficientmice 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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页码:1395 / +
页数:15
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