研究者詳細

顔写真

サンペイ　ソウ
三瓶　想
So Sampei
所属
病院　特殊診療施設　高度救命救急センター
職名
助教
学位

  • 博士（医学）（東北大学）

  • 修士（工学）（明治大学）

論文 14

  1. Endothelial Glycocalyx Disorders May Be Associated With Extended Inflammation During Endotoxemia in a Diabetic Mouse Model. 国際誌

    So Sampei, Hideshi Okada, Hiroyuki Tomita, Chihiro Takada, Kodai Suzuki, Takamasa Kinoshita, Ryo Kobayashi, Hirotsugu Fukuda, Yuki Kawasaki, Ayane Nishio, Hirohisa Yano, Isamu Muraki, Yohei Fukuda, Keiko Suzuki, Nagisa Miyazaki, Takatomo Watanabe, Tomoaki Doi, Takahiro Yoshida, Akio Suzuki, Shozo Yoshida, Shigeki Kushimoto, Shinji Ogura

    Frontiers in cell and developmental biology　9　623582-623582　2021年

    DOI： 10.3389/fcell.2021.623582 　

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    In diabetes mellitus (DM) patients, the morbidity of infectious disease is increased, and these infections can easily progress from local to systemic infection. Sepsis is a characteristic of organ failure related to microcirculation disorders resulting from endothelial cell injury, whose most frequent comorbidity in patients is DM. The aim of the present study was to evaluate the influence of infection on DM-induced microvascular damage on inflammation and pulmonary endothelial structure using an experimental endotoxemia model. Lipopolysaccharide (LPS; 15 mg/kg) was injected intraperitoneally into 10-week-old male C57BLKS/J Iar- + lepr db /lepr db (db/db) mice and into C57BLKS/J Iar-m + / + lepr db (db/ +) mice, which served as the littermate non-diabetic control. At 48 h after LPS administration, the survival rate of db/db mice (0%, 0/10) was markedly lower (P < 0.05) than that of the db/ + mice (75%, 18/24), whereas the survival rate was 100% in both groups 24 h after LPS administration. In control mice, CD11b-positive cells increased at 6 h after LPS administration; by comparison, the number of CD11b-positive cells increased gradually in db/db mice until 12 h after LPS injection. In the control group, the number of Iba-1-positive cells did not significantly increase before and at 6, 12, and 24 h after LPS injection. Conversely, Iba-1-positive cells continued to increase until 24 h after LPS administration, and this increase was significantly greater than that in the control mice. Expression of Ext1, Csgalnact1, and Vcan related to endothelial glycocalyx synthesis was significantly lower in db/db mice than in the control mice before LPS administration, indicating that endothelial glycocalyx synthesis is attenuated in db/db/mice. In addition, ultrastructural analysis revealed that endothelial glycocalyx was thinner in db/db mice before LPS injection. In conclusion, in db/db mice, the endothelial glycocalyx is already injured before LPS administration, and migration of inflammatory cells is both delayed and expanded. This extended inflammation may be involved in endothelial glycocalyx damage due to the attenuation of endothelial glycocalyx synthesis.

  2. Dynamic and functional changes in vascular endothelial cell monolayers under combined hypoxic and inflammatory stimuli. 国際誌

    Kazuki Sone, Ai Funatsu, So Sampei, Kenichi Funamoto

    Scientific reports　2025年12月10日

    DOI： 10.1038/s41598-025-31172-1 　

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    In sepsis, dysregulated inflammatory responses cause microthrombi formation, leading to organ hypoxia. While endothelial cell (EC) responses to inflammation are well-studied, the combined effects of hypoxia and inflammation remain unclear. We investigated EC dynamics and function under simultaneous hypoxia and lipopolysaccharide (LPS) exposure using microfluidic devices with controllability of oxygen concentration. Collective cell migration was measured by particle image velocimetry, while monolayer permeability was assessed by diffusion of fluorescently labeled dextran. Additionally, we examined adhesion and signaling protein expression. Migration speed decreased under approximately 1% O2, but LPS exposure delayed this decrease, attenuating hypoxic responses. Both hypoxia and LPS increased permeability, though this effect was partially suppressed by LPS preconditioning at a specific concentration. LPS exposure increased ICAM-1 and VCAM-1 expression on endothelial surfaces, except for VCAM-1 under hypoxia, suggesting complex interactions between HIF-1α and NF-κB pathways activated by hypoxia and LPS, respectively. NF-κB inhibition suppressed both collective migration and permeability, confirming its role in these dynamic and functional changes. These findings provide novel insights into EC phenotypic alterations under combined hypoxic and inflammatory conditions in an in vitro model that effectively recapitulates key aspects of sepsis pathophysiology.

  3. 敗血症を研究する:Challenge & Breakthrough グリコカリックス構成成分の事前投与はLPS投与糖尿病マウスの転帰を改善する

    三瓶 想, 岡田 英志, 工藤 大介

    日本救急医学会雑誌　36　(11)　820-820　2025年11月

    出版者・発行元： (一社)日本救急医学会

    ISSN：0915-924X

    eISSN：1883-3772

  4. Serum syndecan-1 concentration in hospitalized patients with heart failure may predict readmission-free survival. 国際誌

    Yuichiro Kitagawa, Itta Kawamura, Keiko Suzuki, Hideshi Okada, Takuma Ishihara, Hiroyuki Tomita, Kodai Suzuki, Chihiro Takada, So Sampei, Soichiro Kano, Kohei Kondo, Hirotaka Asano, Yugo Wakayama, Ryo Kamidani, Yuki Kawasaki, Hirotsugu Fukuda, Ayane Nishio, Takahito Miyake, Tetsuya Fukuta, Ryu Yasuda, Hideaki Oiwa, Yoshinori Kakino, Nagisa Miyazaki, Takatomo Watanabe, Takahiro Yoshida, Tomoaki Doi, Akio Suzuki, Shozo Yoshida, Hitoshi Matsuo, Shinji Ogura

    PloS one　16　(12)　e0260350　2021年

    DOI： 10.1371/journal.pone.0260350 　

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    Syndecan-1 is found in the endothelial glycocalyx and is released into the bloodstream during stressed conditions, including severe diseases such as acute kidney injury, chronic kidney disease, and cardiovascular disease. This study investigated the prognostic value of serum syndecan-1 concentration in patients with heart failure upon admission. Serum syndecan-1 concentration was analyzed in 152 patients who were hospitalized for worsening heart failure from September 2017 to June 2018. The primary outcome of the study was readmission-free survival, defined as the time from the first admission to readmission for worsened heart failure or death from any cause, which was assessed at 30 months after discharge from the hospital. The secondary outcome of the study was survival time. Blood samples and echocardiogram data were analyzed. Univariate and multivariable time-dependent Cox regression analyses adjusted for age, creatinine levels, and use of antibiotics were conducted. The serum syndecan-1 concentration was significantly associated with readmission-free survival. Subsequently, the syndecan-1 concentration may have gradually decreased with treatment. The administration of human atrial natriuretic peptide and antibiotics may have modified the relationship between readmission-free survival and serum syndecan-1 concentration (p = 0.01 and 0.008, respectively). Serum syndecan-1 concentrations, which may indicate injury to the endothelial glycocalyx, predict readmission-free survival in patients with heart failure.

  5. 糖尿病では敗血症性血管炎下で炎症細胞の遊走が増加する

    三瓶 想, 岡田 英志, 鈴木 浩大, 岡本 遥, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省三, 久志本 成樹, 小倉 真治

    日本集中治療医学会雑誌　27　(Suppl.)　428-428　2020年9月

    出版者・発行元： (一社)日本集中治療医学会

    ISSN：1340-7988

    eISSN：1882-966X

  6. Neutrophil Elastase Inhibition Ameliorates Endotoxin-induced Myocardial Injury Accompanying Degradation of Cardiac Capillary Glycocalyx. 国際誌

    Tetsuya Fukuta, Hideshi Okada, Genzou Takemura, Kodai Suzuki, Chihiro Takada, Hiroyuki Tomita, Akio Suzuki, Kazumasa Oda, Akihiro Uchida, Saori Matsuo, Hirotsugu Fukuda, Hirohisa Yano, Isamu Muraki, Ryogen Zaikokuji, Ayumi Kuroda, Ayane Nishio, So Sampei, Nagisa Miyazaki, Yasuaki Hotta, Noriaki Yamada, Takatomo Watanabe, Kentaro Morishita, Tomoaki Doi, Takahiro Yoshida, Hiroaki Ushikoshi, Shozo Yoshida, Yoichi Maekawa, Shinji Ogura

    Shock (Augusta, Ga.)　54　(3)　386-393　2020年9月

    DOI： 10.1097/SHK.0000000000001482 　

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    Myocardial injury in sepsis may be caused by a burst of several inflammatory mediators, leading to vascular endothelial injuries. However, the contribution of neutrophil elastase (NE) to myocardial injury in sepsis is still unknown. We aimed to evaluate whether endotoxemia-induced myocardial injury is associated with NE. Lipopolysaccharide (LPS) was injected intraperitoneally at a dose of 20 mg/kg into granulocyte-colony-stimulating-factor knockout mice (G-CSF-KO), which have few neutrophils, and littermate control mice. The survival rate of G-CSF-KO mice 48 hours after LPS injection was significantly greater than that of control mice. The serum level of troponin I in G-CSF-KO mice was significantly lower than that in control mice. In addition, the concentration of inflammatory cytokine interleukin-6 (IL-6) was significantly decreased 6 and 12 hours after LPS administration compared with that in control mice. Ultrastructural analysis revealed that vascular endothelial structures and the endothelial glycocalyx in G-CSF-KO mice were clearly preserved. Next, mice were injected with 0.2 mg/kg sivelestat (an NE inhibitor) after LPS administration. The survival rate was significantly higher and the serum level of troponin I was lower in sivelestat-injected mice than in control mice, respectively. Furthermore, IL-6 levels were significantly decreased 6 and 12 hours after LPS administration compared with those in control mice. Vascular endothelial structures and the endothelial glycocalyx in sivelestat-treated mice were clearly preserved at the ultrastructural level. In conclusion, NE is significantly associated with myocardial injury in endotoxemia. Inhibition of NE may be a useful tool for the management of endotoxemia.

  7. Ultrastructural alteration of pulmonary tissue under conditions of high oxygen concentration. 国際誌

    Hirohisa Yano, Ayumi Kuroda, Hideshi Okada, Hiroyuki Tomita, Kodai Suzuki, Chihiro Takada, Hirotsugu Fukuda, Yuki Kawasaki, Isamu Muraki, Yugo Wakayama, Soichiro Kano, Yuto Tamaoki, Ayane Nishio, Risa Inagawa, So Sampei, Ryo Kamidani, Yoshinori Kakino, Ryu Yasuda, Yuichiro Kitagawa, Tetsuya Fukuta, Takahito Miyake, Norihide Kanda, Nagisa Miyazaki, Tomoaki Doi, Takahiro Yoshida, Akio Suzuki, Shozo Yoshida, Shinji Ogura

    International journal of clinical and experimental pathology　13　(12)　3004-3012　2020年

    eISSN：1936-2625

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    OBJECTIVE: To determine the structure of pulmonary tissue under conditions of high oxygen concentration. METHODS: Ten-week-old C57BL male mice and control mice were exposed to 100% oxygen and to room air for 72 hours, respectively. To follow the progression of lesions, the mice were sacrificed at 6, 12, 24, 48, and 72 hours after 100% oxygen administration. Lung specimens obtained from these mice underwent morphologic analysis and immunofluorescence studies. We used scanning and transmission electron microscopy to determine the ultrastructure of the pulmonary capillaries, including the endothelial glycocalyx. To visualize the endothelial glycocalyx, we performed lanthanum nitrate staining. RESULTS: The survival rate of the 100% oxygen administration group was 5% (2/40) and that of the control group was 100%. Perivascular cavity enlargement was detected 12 hours after 100% oxygen administration and expanded over time. Ultrastructural analysis using electron microscopy revealed collapsed alveoli and pulmonary capillary wall and alveolar wall thickening in the 100% oxygen group. The pulmonary capillary endothelial glycocalyx was injured in the 100% oxygen group. The perivascular cavity decreased in mice that were returned to room air after 48 hours of 100% oxygen administration. CONCLUSION: High-concentration oxygen causes perivascular cavity enlargement; this is thought to be a special characteristic of high oxygen damage. In addition, high-concentration oxygen may be involved in pulmonary endothelial glycocalyx injury.

  8. 糖尿病マウス敗血症性血管炎モデルにおける血管内皮グリコカリックスの障害と炎症への関与

    三瓶 想, 岡田 英志, 鈴木 浩大, 福田 哲也, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省造, 久志本 成樹, 小倉 真治

    日本救急医学会雑誌　30　(9)　680-680　2019年9月

    出版者・発行元： (一社)日本救急医学会

    ISSN：0915-924X

    eISSN：1883-3772

  9. Factors Enhancing Serum Syndecan-1 Concentrations: A Large-Scale Comprehensive Medical Examination. 国際誌

    Kazumasa Oda, Hideshi Okada, Akio Suzuki, Hiroyuki Tomita, Ryo Kobayashi, Kazuyuki Sumi, Kodai Suzuki, Chihiro Takada, Takuma Ishihara, Keiko Suzuki, Soichiro Kano, Kohei Kondo, Yuki Iwashita, Hirohisa Yano, Ryogen Zaikokuji, So Sampei, Tetsuya Fukuta, Yuichiro Kitagawa, Haruka Okamoto, Takatomo Watanabe, Tomonori Kawaguchi, Takao Kojima, Fumiko Deguchi, Nagisa Miyazaki, Noriaki Yamada, Tomoaki Doi, Takahiro Yoshida, Hiroaki Ushikoshi, Shozo Yoshida, Genzou Takemura, Shinji Ogura

    Journal of clinical medicine　8　(9)　2019年8月27日

    DOI： 10.3390/jcm8091320 　

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    Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.

  10. Neutrophil Elastase Damages the Pulmonary Endothelial Glycocalyx in Lipopolysaccharide-Induced Experimental Endotoxemia. 国際誌

    Kodai Suzuki, Hideshi Okada, Genzou Takemura, Chihiro Takada, Ayumi Kuroda, Hirohisa Yano, Ryogen Zaikokuji, Kentaro Morishita, Hiroyuki Tomita, Kazumasa Oda, Saori Matsuo, Akihiro Uchida, Tetsuya Fukuta, So Sampei, Nagisa Miyazaki, Tomonori Kawaguchi, Takatomo Watanabe, Takahiro Yoshida, Hiroaki Ushikoshi, Shozo Yoshida, Yoichi Maekawa, Shinji Ogura

    The American journal of pathology　189　(8)　1526-1535　2019年8月

    DOI： 10.1016/j.ajpath.2019.05.002 　

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    Neutrophil elastase (NE) is necessary for effective sterilization of phagocytosed bacterial and fungal pathogens; however, NE increases alveolocapillary permeability and induces proinflammatory cytokine production in sepsis-induced acute respiratory distress syndrome. Under septic conditions, the pulmonary endothelial glycocalyx covering on the healthy endothelium surface is injured, but the contribution of NE to this injury remains unknown. Our aim was to examine whether NE-induced pulmonary endothelial injury is associated with endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 9- to 12-week-old granulocyte colony-stimulating factor knockout (G-CSFKO) mice, which harbor few neutrophils, and littermate control mice; in a second assay, mice were injected with the NE-inhibitor sivelestat (0.2 mg/kg) at 3, 6, 9, and 12 hours after LPS administration. Subsequently, vascular endothelial injury was evaluated through ultrastructural analysis. At 48 hours after LPS injection, survival rate was more than threefold higher among G-CSFKO than control mice, and degradation of both thrombomodulin and syndecan-1 was markedly attenuated in G-CSFKO compared with control mice. Ultrastructural analysis revealed attenuated vascular endothelial injury and clear preservation of the endothelial glycocalyx in G-CSFKO mice. Moreover, after LPS exposure, survival rate was approximately ninefold higher among sivelestat-injected mice than control mice, and sivelestat treatment potently preserved vascular endothelial structures and the endothelial glycocalyx. In conclusion, NE is associated with pulmonary endothelial injury under LPS-induced endotoxemic conditions.

  11. 糖尿病モデルマウスにおける敗血症性血管炎の超微形態の検討

    三瓶 想, 岡田 英志, 鈴木 浩大, 福田 哲也, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省造, 久志本 成樹, 小倉 真治

    日本集中治療医学会雑誌　26　(Suppl.)　[O22-2]　2019年2月

    出版者・発行元： (一社)日本集中治療医学会

    ISSN：1340-7988

    eISSN：1882-966X

  12. 糖尿病と血管内皮グリコカリックスの超微形態

    福田 洋丞, 岡田 英志, 鈴木 浩大, 三瓶 想, 福田 哲也, 岡本 遥, 川口 智則, 吉田 隆浩, 牛越 博昭, 吉田 省造, 小倉 真治

    日本救急医学会雑誌　29　(10)　442-442　2018年10月

    出版者・発行元： (一社)日本救急医学会

    ISSN：0915-924X

    eISSN：1883-3772

  13. 血管攣縮像を経時的に捉えた典型的可逆性脳血管攣縮症候群の一例． 査読有り

    三瓶想, 川口奉洋, 中川敦寛, 野村亮介, 冨永悌二, 久志本成樹

    日本救急医学会雑誌　27　(6)　2016年7月

    DOI： 10.1002/jja2.12102 　

  14. Granulomatosis with polyangiitis preceded by central diabetes insipidus.

    So Sampei, Ryu Watanabe, Tomonori Ishii, Hideo Harigae

    Internal medicine (Tokyo, Japan)　53　(15)　1725-6　2014年

    eISSN：1349-7235

︎全件表示 ︎最初の5件までを表示

MISC 5

  1. 糖尿病モデルマウスのグリコカリックス障害と敗血症性血管炎下における炎症細胞の遊走遅延

    三瓶 想, 岡田 英志, 鈴木 浩大, 岡本 遥, 土井 智章, 三宅 喬人, 福田 哲也, 北川 雄一郎, 吉田 省造, 久志本 成樹, 小倉 真治

    日本救急医学会雑誌　31　(11)　969-969　2020年11月

    出版者・発行元： (一社)日本救急医学会

    ISSN： 0915-924X

    eISSN： 1883-3772

  2. 糖尿病では敗血症性血管炎下で炎症細胞の遊走が増加する

    三瓶 想, 岡田 英志, 鈴木 浩大, 岡本 遥, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省三, 久志本 成樹, 小倉 真治

    日本集中治療医学会雑誌　27　(Suppl.)　428-428　2020年9月

    出版者・発行元： (一社)日本集中治療医学会

    ISSN： 1340-7988

    eISSN： 1882-966X

  3. 糖尿病マウス敗血症性血管炎モデルにおける血管内皮グリコカリックスの障害と炎症への関与

    三瓶 想, 岡田 英志, 鈴木 浩大, 福田 哲也, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省造, 久志本 成樹, 小倉 真治

    日本救急医学会雑誌　30　(9)　680-680　2019年9月

    出版者・発行元： (一社)日本救急医学会

    ISSN： 0915-924X

  4. 敗血症性肺血管炎におけるリコンビナントアンチトロンビンの血管内皮保護効果の検討

    村木 勇, 岡田 英志, 鈴木 浩大, 高田 ちひろ, 三瓶 想, 福田 哲也, 矢野 博久, 土井 智章, 熊田 恵介, 吉田 省造, 小倉 真治

    Shock: 日本Shock学会雑誌　34　(1)　63-63　2019年6月

    出版者・発行元： (一社)日本Shock学会

    ISSN： 0919-8156

    eISSN： 2185-8225

  5. 糖尿病マウス敗血症性血管炎モデルにおける血管内皮グリコカリックスの超微形態評価

    三瓶 想, 岡田 英志, 鈴木 浩大, 高田 ちひろ, 福田 哲也, 土井 智章, 熊田 恵介, 牛越 博昭, 吉田 省造, 久志本 成樹, 小倉 真治

    Shock: 日本Shock学会雑誌　34　(1)　66-66　2019年6月

    出版者・発行元： (一社)日本Shock学会

    ISSN： 0919-8156

    eISSN： 2185-8225

共同研究・競争的資金等の研究課題 2

  1. 血管内皮グリコカリックス断片による、炎症促進および収束の2面性に関する検討

    三瓶 想

    2023年4月1日 ～ 2027年3月31日

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    敗血症は重症感染症の一つで、その本態は高サイトカイン血症を伴う微小血管障害である。死亡数も上昇傾向にあるが治療法は未だ確立されていない。本研究は高サイトカイン血症の原因として血管内皮細胞障害に着目し、それを保護する血管内皮グリコカリックスの関与について検討を行う。 血管内皮グリコカリックスは多彩な機能を有し、炎症にも関与する。特にその断片はdamage associated molecular patterns（DAMPs）としてtoll like receptor4（TLR4）と結合し炎症を促進する働きがある一方、high mobility group box 1（HMGB1）やヒストンなどの DAMPsを吸着する機能がある。そこで本研究ではこの血管内皮グリコカリックス断片の相反する機能に着目し、「血中の血管内皮グリコカリックス断片の量により、炎症を促進する方向から収束する方向に切替わるのではないか」と仮説を置き検討を行っている。 まず初めに野生型モデルマウスに惹起する炎症強度を決めるため、LPSの投与量について検討を行った。野生型マウスに対し、LPS 20mg/kgを腹腔内投与したところ、36～72時間後に全て死亡した。続いてLPSを 15 mg/kgに減量し、再度評価したが36～48時間後に全て死亡した。これは以前使用していたLPSとLotが変わったことによる影響と考えられた。

  2. 糖尿病患者の感染症重症化機序の解明：血管内皮細胞pyroptosisによるIL-1β放出

    三瓶 想

    提供機関：Japan Society for the Promotion of Science

    制度名：Grants-in-Aid for Scientific Research

    研究種目：Grant-in-Aid for Research Activity Start-up

    研究機関：Tohoku University

    2022年8月31日 ～ 2024年3月31日

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    糖尿病モデルマウスおよび対照群の野生型マウスにLPSを用いて炎症を惹起し、6時間後にsacrificeした両マウスの肺および心臓、腎臓、肝臓について抗IL-1β抗体を用いて免疫組織染色した。肺と心臓ではほとんどIL-1β陽性細胞が確認できなかったが、腎臓と肝臓において陽性細胞の集積が確認された。また血管内皮細胞のpyroptosisについて評価するため、抗CD31抗体と抗Caspase-1抗体および抗NLRP3抗体を用いて蛍光二重免疫染色を施行したところ、Caspase-1およびNLRP3が肺と腎臓の血管内皮細胞と共局在することが分かった。