期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 138, 期 5, 页码 1395-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2016.01.032
关键词
Airway inflammation; asthma; eosinophil; IL-33; papain; platelet
资金
- National Institute of Biomedical Innovation grant [10-43]
- National Center for Child Health and Development [26-9, 26-46]
- JSPS KAKENHI grant [23591666]
- Grants-in-Aid for Scientific Research [16K15515, 15K15377, 23591666, 15K09560, 15H04866] Funding Source: KAKEN
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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