研究等業績 - 原著論文 - 植木 重治
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A case of eosinophilic granulomatosis with polyangiitis preceded by allergic bullous lesions
Hasegawa E.
Modern Rheumatology Case Reports ( Modern Rheumatology Case Reports ) 9 ( 1 ) 143 - 148 2025年01月
研究論文（学術雑誌）
A 62-year-old man with a history of diabetes mellitus was hospitalised with numbness of lower limbs, bullous lesions of the whole body, kidney dysfunction, presence of eosinophils, and elevated antineutrophil cytoplasmic antibodies to myeloperoxidase and anti-bullous pemphigoid 180 antibodies and was diagnosed with mononeuritis multiplex. Kidney and muscle biopsies showed vasculitis with fibrinoid necrosis, whereas skin biopsies showed only blister formation between the epidermis and dermis; a high eosinophilic infiltrate was present in all three tissues. These findings led to a diagnosis of eosinophilic granulomatosis with polyangiitis combined with allergic bullous lesions. Immunohistological examination indicated cytolytic eosinophils and extracellular traps, suggesting the presence of eosinophil extracellular trap cell death (eosinophil ETosis) in diseased tissue.
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Miyabe Y.
Journal of Allergy and Clinical Immunology ( Journal of Allergy and Clinical Immunology ) 2024年
研究論文（学術雑誌）
BACKGROUND: Airway obstruction caused by viscous mucus is an important pathophysiological characteristic of persistent inflammation, which can result in organ damage. OBJECTIVE: We investigated the hypothesis that the biophysical characteristics of accumulating granulocytes impact the clinical properties of mucus. METHODS: Surgically acquired nasal mucus samples from patients with eosinophilic chronic rhinosinusitis and neutrophil-dominant, non-eosinophilic chronic rhinosinusitis were evaluated in terms of computed tomography density, viscosity, water content, wettability, and protein composition. Isolated human eosinophils and neutrophils were stimulated to induce the formation of extracellular traps, followed by the formation of aggregates. The biophysical properties of the aggregated cells were also examined. RESULTS: Mucus from patients with eosinophilic chronic rhinosinusitis had significantly higher computed tomography density, viscosity, dry weight, and hydrophobicity compared with mucus from patients with non-eosinophilic chronic rhinosinusitis. The levels of eosinophil-specific proteins in mucus correlated with its physical properties. Eosinophil and neutrophil aggregates showed physical and pathological characteristics resembling those of mucus. Co-treatment with deoxyribonuclease and heparin, which slenderizes the structure of eosinophil extracellular traps, efficiently induced reductions in the viscosity and hydrophobicity of both eosinophil aggregates and eosinophilic mucus. CONCLUSIONS: The present study elucidates the pathogenesis of mucus stasis in infiltrated granulocyte aggregates from a novel perspective. These findings may contribute to the development of treatment strategies for eosinophilic airway diseases.
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Rapidly progressive mucus plugs in allergic bronchopulmonary mycosis
Miyazaki O.
Journal of Asthma ( Journal of Asthma ) 1 - 9 2024年
研究論文（学術雑誌）
INTRODUCTION: Allergic bronchopulmonary mycosis (ABPM) is a chronic airway disease characterized by the presence of fungi that trigger allergic reactions and airway obstruction. Here, we present a unique case of ABPM in which a patient experienced sudden respiratory failure due to mucus plug-induced airway obstruction. The patient's life was saved by venovenous extracorporeal membrane oxygenation (VV-ECMO) and bronchoscopic removal of the plug. This case emphasizes the clinical significance of mucus plug-induced airway obstruction in the differential diagnosis of respiratory failure in patients with ABPM. CASE STUDY: A 52-year-old female clerical worker with no smoking history, presented with dyspnea. CT scan revealed mucus plugs in both lungs. Despite treatment, the dyspnea progressed rapidly to respiratory failure, leading to VV-ECMO placement. RESULTS: CT revealed bronchial wall thickening, obstruction, and extensive atelectasis. Bronchoscopy revealed extensive mucus plugs that were successfully removed within two days. The patient's respiratory status significantly improved. Follow-up CT revealed no recurrence. Fungal cultures identified Schizophyllum commune, confirming ABPM. Histological examination of the mucus plugs revealed aggregated eosinophils, eosinophil granules, and Charcot-Leyden crystals. Galectin-10 and major basic protein (MBP) staining supported these findings. Eosinophil extracellular traps (EETs) and eosinophil cell death (ETosis), which contribute to mucus plug formation, were identified by citrullinated histone H3 staining. CONCLUSION: Differentiating between asthma exacerbation and mucus plug-induced airway obstruction in patients with ABPM and those with acute respiratory failure is challenging. Prompt evaluation of mucous plugs and atelectasis using CT and timely decision to introduce ECMO and bronchoscopic mucous plug removal are required.
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Sato T.
Journal of Dermatological Science ( Journal of Dermatological Science ) 112 ( 1 ) 6 - 14 2023年10月
研究論文（学術雑誌）
BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease in which abundant eosinophils accumulate in the blisters. Galectin-10 abounds in the cytoplasm of eosinophils and is released as a result of eosinophil extracellular trap cell death (EETosis). OBJECTIVE: To identify EETosis and the pathological roles of galectin-10 in BP. METHODS: EETosis and galectin-10 in BP blisters were confirmed by immunofluorescence and transmission electron microscopy. The concentrations of galectin-10 in serum and blister fluid from BP patients were studied by ELISA. The matrix metalloproteinase (MMP) expression in BP blisters was immunohistochemically compared to that in healthy controls. As an in vitro assay, normal human epidermal keratinocytes (NHEKs) and normal human dermal fibroblasts (NHDFs) were stimulated with galectin-10, followed by MMP expression measurement by real-time PCR and ELISA. The signaling pathways activated by galectin-10 were studied using Western blotting and confirmed by inhibition assays. RESULTS: Galectin-10-containing eosinophil infiltration and the extracellular deposition of major basic protein were observed in BP blisters. The ultrastructural characteristics of tissue eosinophils indicated piecemeal degranulation and EETosis. In the BP patients, the concentration of galectin-10 was higher in the blister fluid than in the serum. Several types of MMPs were upregulated in BP blisters. Galectin-10 upregulated the production of MMPs through the pathways of p38 MAPK, ERK and JNK in NHEKs and NHDFs. CONCLUSION: In the BP blisters, the eosinophils underwent EETosis and released galectin-10. Galectin-10 might contribute to BP blister formation through the production of MMPs by keratinocytes and fibroblasts.
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Allergic fungal rhinosinusitis: What we can learn from allergic bronchopulmonary mycosis
Nakayama T.
Allergology International ( Allergology International ) 72 ( 4 ) 521 - 529 2023年10月
研究論文（学術雑誌）
<p>Allergic fungal rhinosinusitis (AFRS) and allergic bronchopulmonary mycosis (ABPM) are inflammatory disorders of the respiratory tract resulting from type 1 and 3 hypersensitivity reactions against fungi. The hallmark features of both diseases are eosinophil infiltration into the airway mucosa caused by localized type 2 inflammation and concomitant viscid secretions in the airways. Eosinophilic mucin-induced compression of adjacent anatomic structures leads to bone erosion and central bronchiectasis in the upper and lower respiratory tracts, respectively. Although these diseases share common features in their pathogenesis, they also exhibit notable differences. Epidemiologic findings are diverse, with AFRS typically presenting at a younger age, exhibiting less complicated bronchial asthma, and displaying lower total immunoglobulin E levels in laboratory findings compared with ABPM. Furthermore, despite their similar pathogenesis, the rarity of sinio-bronchial allergic mycosis in both AFRS and ABPM underscores the distinctions between these two diseases. This review aims to clarify the similarities and differences in the pathogenesis of AFRS and ABPM to determine what can be learned about AFRS from ABPM, where more is known.</p>
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Allergic fungal diseases in the upper and lower airways
Ueki S.
ERS Monograph ( ERS Monograph ) 2022 119 - 140 2022年 [査読有り] [招待有り]
研究論文（学術雑誌） 国内共著
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Hypogranular eosinophils in eosinophilic gastrointestinal disease
Tomizawa H.
International Journal of Laboratory Hematology ( International Journal of Laboratory Hematology ) 2022年 [査読有り]
研究論文（学術雑誌） 国内共著
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Comparison of CD16-negative selection vs. MACSxpress system for isolation of blood eosinophils
Fukuchi Mineyo, Ueki Shigeharu, Saito Hidekazu, Miyabe Yui, Konno Yasunori, Omokawa Ayumi, Saga Tomoo, Moritoki Yuki, Takeda Masahide, Yamada Takechiyo, Hirokawa Makoto
Allergology International ( 一般社団法人日本アレルギー学会 ) 68 ( Supplement.1 ) S11 - S13 2019年 [査読有り]
研究論文（学術雑誌） 国内共著
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Eosinophil extracellular trap cell death-derived DNA traps: Their presence in secretions and functional attributes.
Ueki S, Konno Y, Takeda M, Moritoki Y, Hirokawa M, Matsuwaki Y, Honda K, Ohta N, Yamamoto S, Takagi Y, Wada A, Weller PF
The Journal of allergy and clinical immunology 2015年06月 [査読有り]
研究論文（学術雑誌） 国内共著
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Konno Y, Ueki S, Takeda M, Kobayashi Y, Tamaki M, Moritoki Y, Oyamada H, Itoga M, Kayaba H, Omokawa A, Hirokawa M.
Konno Y, Ueki S, Takeda M, Kobayashi Y, Tamaki M, Moritoki Y, Oyamada H, Itoga M, Kayaba H, Omokawa A, Hirokawa M.
PLoS One. 10 ( 3 ) e0120386. 2015年03月 [査読有り]
研究論文（学術雑誌） 国内共著
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The effect of pharmacological PI3Kg inhibitor on eotaxin-induced human eosinophil functions.
Saito, Y., Takeda, M., Nishikawa, J., Konno, Y., Tamaki, M., Itoga, M., Kobayashi, Y., Moritoki, Y., Ito, W., Chihara, J., Ueki, S.
Pulm Pharmacol Ther. 27 ( 2 ) 164 - 189 2014年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Expression and functional roles of G-protein-coupled estrogen receptor (GPER) in human eosinophils.
Tamaki, M., Konno, Y., Kobayashi, Y., Takeda, M., Itoga, M., Moritoki, Y., Oyamada, H., Kayaba, H., Chihara, J., Ueki, S.
Immunol Lett. 160 ( 1 ) 72 - 78 2014年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Human eosinophils express functional CCR7.
Akuthota, P., Ueki, S., Estanislau, J., Weller, PF.
Am J Respir Cell Mol Biol. 48 ( 6 ) 758 - 764 2013年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans.
Ueki, S., Melo, RC., Ghiran, I., Spencer, LA., Dvorak, AM., Weller, PF.
Blood 121 ( 11 ) 2074 - 2083 2013年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Retinoic acids up-regulate functional eosinophil-driving receptor CCR3.
Ueki, S., Nishikawa, J., Yamauchi, Y., Konno, Y., Tamaki, M., Itoga, M., Kobayashi, Y., Takeda, M., Moritoki, Y., Ito, W, Chihara, J.
Allergy 68 ( 7 ) 953 - 956 2013年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Docosahexaenoic acid exerts anti-inflammatory actions on human eosinophils through PPAR-independent mechanisms.
TanigaiT., Ueki S., Kihara J., Kamada R., Yamauchi Y., Sokal A., Takeda M., Ito W., Kayaba H., Adach,T., Ohta K., Chihara J.
Int.Arch.Allergy Immunol. 158 375 - 386 2012年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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Thiazolidinedieons as potent inducers of hepatocyte growth factor.
Ito W, Ueki S, Takeda M, Tanigai T, Kayaba H, Chihara J.
Hepatology 51 ( 5 ) 1866 - 1867 2010年01月 [査読有り]
研究論文（学術雑誌） 国内共著
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肥満が喘息の病態に及ぼす影響
植木重治,茆原順一
呼吸器内科 17 ( 6 ) 504 - 510 2010年01月 [招待有り]
研究論文（学術雑誌） 国内共著
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ビタミンA・局所で産生されるレチノイン酸とアレルギー
植木重治, 糸賀正道, 茆原順一.
臨床免疫・アレルギー科 54 ( 3 ) 293 - 299 2010年01月 [招待有り]
研究論文（学術雑誌） 国内共著
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施設間ネットワークによる細菌検査データベース(Akita-ReNICS)の構築．
植木重治, 萱場広之，茆原順一
Medical Technology 38 ( 11 ) 1073 - 1074 2010年01月
研究論文（学術雑誌） 国内共著