Journal of thrombosis and haemostasis : JTH · 2025
Deficiencies of carboxypeptidase N and carboxypeptidase B2 have opposite effects in a virulent mouse E. coli sepsis model.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhou Qin, Nishimura Toshihiko, Veer Cornelis van 't, Leung Lawrence L, Morser John
Аннотация
BACKGROUND: Two basic carboxypeptidases circulate in plasma, procarboxypeptidase B2, which is activated to carboxypeptidase B2 (CPB2), and carboxypeptidase N (CPN). These enzymes inactivate complement anaphylatoxins, C3a and C5a, with high C5a being toxic.
OBJECTIVES: To test the hypothesis that these carboxypeptidases would affect Escherichia coli sepsis in mice differently because CPN is constitutively active while procarboxypeptidase B2 beeds to be locally activated.
METHODS: Mice deficient in CPB2, CPN, or both enzymes were infected with E. coli and their health and survival was compared to wild-type mice. Clinical chemistry, complete blood count, and bacterial load were assessed.
RESULTS: Lack of CPB2 prolonged survival while lack of CPN shortened survival compared to wild-type mice. Liver damage was higher in double deficient mice that were also thrombocytopenic, and CPN-deficient mice were leukopenic. Bacterial load was higher in CPB2 and double deficient mice and lower in CPN-deficient mice.
CONCLUSION: CPN provides first-line protection against excessive C3a and C5a, accounting for the shortened survival in CPN-deficient mice in this sepsis model, despite reduced E. coli load. CPB2 serves a supportive role by primarily inactivating C3a locally. Apparently, CPB2 deficiency led to enhanced local levels of protective C3a and prolonged survival in the CPB2-deficient mice in this model, while the lack of CPN exacerbated the infection.
OBJECTIVES: To test the hypothesis that these carboxypeptidases would affect Escherichia coli sepsis in mice differently because CPN is constitutively active while procarboxypeptidase B2 beeds to be locally activated.
METHODS: Mice deficient in CPB2, CPN, or both enzymes were infected with E. coli and their health and survival was compared to wild-type mice. Clinical chemistry, complete blood count, and bacterial load were assessed.
RESULTS: Lack of CPB2 prolonged survival while lack of CPN shortened survival compared to wild-type mice. Liver damage was higher in double deficient mice that were also thrombocytopenic, and CPN-deficient mice were leukopenic. Bacterial load was higher in CPB2 and double deficient mice and lower in CPN-deficient mice.
CONCLUSION: CPN provides first-line protection against excessive C3a and C5a, accounting for the shortened survival in CPN-deficient mice in this sepsis model, despite reduced E. coli load. CPB2 serves a supportive role by primarily inactivating C3a locally. Apparently, CPB2 deficiency led to enhanced local levels of protective C3a and prolonged survival in the CPB2-deficient mice in this model, while the lack of CPN exacerbated the infection.