東端 晃

While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.

Vibrio vulnificus (V. vulnificus)は，世界中の沿岸海水中に広く生息し，本菌に汚染された魚介類の生食や創傷からの菌の侵入により感染する．発熱，四肢の壊死性筋膜炎等の症状を呈し，短期間で死に至る極めて予後不良の疾患である．V. vulnificus感染症患者の多くは基礎疾患に肝硬変や肝癌等の肝機能障害を有する．日和見感染症である本症において有効なワクチンの開発が重要であり，免疫原性の高い抗原の同定が必要である．今回我々は，V. vulnificusのヒト血清における免疫原性の高い抗原を確認することを目的とし，V. vulnificus感染症患者10名の血清を用いた菌溶解液(V. vulnificus7株，V. parahaemolyticus1株)のimmunoblottingを施行し，感染による抗体産生を分析した．発症時からすでに見られる62-kDaのbandは，患者のみならずV. vulnificus感染症未発症の慢性肝機能障害者及び肝機能正常者のいずれの血清を用いたimmunoblottingにおいても共通して認められた．また，Escherichia.coliやKlebsiella pneumoniaeを用いたimmunoblottingにおいても同様の反応を認め，交差反応を起こしている可能性も考えられた．今回の実験から，V. vulnificusの62-kDaの蛋白がヒトにおける免疫原性の高い抗原の一つであることが予想された．Vibrio vulnificus infection can cause necrotizing fasciitis and sepsis and can develop within a few days despite intensive care. The mortality rate is up to 60% in vulnerable people. Most patients infected with this microbe have chronic liver disease, especially liver cirrhosis or cancer, as an underlying disease. V. vulnificus infection is opportunistic, and there is an urgent need to develop an anti-V. vulnificus vaccine. Thus, it is important to identify immunogenic antigens. We collected human sera from three subject groups : patients with V. vulnificus infection, patients with chronic liver disease but without V. vulnificus infection, and healthy volunteers with normal liver function. Immunoblots of cytosolic and membrane proteins of seven strains of V. vulnificus and one of V. parahaemolyticus were performed with sera from these groups. Although we could not demonstrate differences in antibody response between the groups, all sera showed a strong antibody response to a 62-kDa protein that was common to all strains examined. Immunoblots of Escherichia coli and Klebsiella pneumoniae also showed strong antibody response to this 62-kDa protein, and the possibility of cross-reaction cannot be denied. We identified this 62-kDa protein as an immunogenic antigen of V. vulnificus for humans.