L11
Platelets Constitutively Express Interleukin-33 Protein
Tuesday, March 4, 2014
Exhibit Hall B (Convention Center)
Tomohiro Takeda, MT, PhD., Hirotoshi Unno, M.D., Hideaki Morita, MD., PhD., Hirohisa Saito, MD., PhD., Kenji Matsumoto, MD, PhD, Akio Matsuda, Ph.D.
Rationale: Recent studies revealed that platelets are activated during asthma exacerbation and that depletion of platelets in a mouse model of asthma improves airway inflammation. However, the precise mechanisms of how platelets—despite being devoid of a nucleus—regulate allergic inflammation are not fully understood. IL-33, an IL-1 family cytokine, has attracted attention as a critical cytokine in the development of allergic diseases because of its potent ability to induce type 2 immunity and its strong genetic association with asthma.

Objective: To determine whether platelets express IL-33 protein.

Methods: IL-33 protein in human platelets and a megakaryocyte cell line, MEG-01, and in bone marrow-derived mouse megakaryocytes was detected by Western blot analysis and fluorescent immunostaining. Papain inhalation (100 mg/day x 3 days)-induced IL-33-dependent airway inflammation (Oboki K. et al. PNAS 2010) was compared between platelet-intact and platelet-depleted (by injection of anti-CD41 mAb) groups.

Results: Human platelets and anucleated fragments of mouse bone-marrow-derived megakaryocytes expressed full-length IL-33 protein, which is biologically active. Cytosol, but not nuclear, fractions of MEG-01 and mouse megakaryocytes also expressed full-length IL-33 protein. Depletion of platelets resulted in a significant decrease in eosinophilic, but not neutrophilic, inflammation in papain-treated mouse airways.

Conclusions: Our novel findings suggest that platelets constitutively express active IL-33 protein and that activation of platelets plays a pivotal role in IL-33-dependent type II airway inflammation. Further understanding of the precise molecular mechanisms may lead to platelets’ becoming an attractive new target in asthma treatment.