The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells
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DOI：
10.1159/000515333
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发表时间：
2021-05-04
影响因子：
5.3
通讯作者：
Seki, Shuhji
中科院分区：
文献类型：
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作者：
Kinoshita, Manabu;Ito, Seigo;Seki, Shuhji
用合成的C-反应蛋白（CRP）（一种功能性CRP肽）预处理，有可能通过细菌攻击增强巨噬细胞的吞噬作用。然而，后治疗在临床上是理想的。我们研究了合成CRP后处理对小鼠盲肠结扎穿孔（CLP）的疗效，重点是肝巨噬细胞。小鼠接受CLP，1小时后，腹膜内施用合成CRP或盐水。用合成CRP后处理增加CLP后小鼠存活。CLP后24小时，它减少了肝脏中的活菌计数，枯否细胞数量增加，但单核细胞衍生的肝脏巨噬细胞数量没有增加。用合成的CRP后处理增加枯否细胞对大肠杆菌（E. coli）以及肺炎克雷伯菌（Klebsiella pneumoniae）。合成CRP治疗增加了E.大肠杆菌吞噬枯否细胞，导致24 h肝脏组织TNF水平升高。枯否细胞基本上表达Fc γ RI，其是CRP的配体，并且它们的Fc γ RI表达在CLP后进一步增加。相比之下，合成CRP治疗既不影响单核细胞衍生的肝巨噬细胞的吞噬功能（显示弱Fc γ RI表达），也不影响其TNF产生。小鼠枯否细胞的耗竭抑制了CLP小鼠中合成CRP的这些有益作用。结论：合成CRP后处理通过激活表达Fc γ RI的枯否细胞的吞噬作用有效改善了鼠细菌性腹膜炎。
Pretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and puncture (CLP), focusing on liver macrophages. Mice received CLP, and 1 h later, synthetic CRP or saline was intraperitoneally administered. Posttreatment with synthetic CRP increased the murine survival after CLP. It reduced viable bacterial counts in the liver 24 h after CLP with an increase in the number of Kupffer cells but not monocyte-derived liver macrophages. Posttreatment with synthetic CRP increased the phagolytic activity of Kupffer cells against Escherichia coli (E. coli) as well as capsulated Klebsiella pneumoniae at 3 h after CLP. Synthetic CRP therapy augmented TNF production by E. coli-phagocytosing Kupffer cells, resulting in an increase in tissue TNF levels in the liver at 24 h. Kupffer cells substantially expressed Fc gamma RI, which is a ligand of CRP, and their Fc gamma RI expression was further increased after CLP. In contrast, synthetic CRP therapy affected neither the phagocytic function of monocyte-derived liver macrophages (showing a weak Fc gamma RI expression) nor their TNF production. Depletion of Kupffer cells in mice inhibited these beneficial effects of synthetic CRP in CLP mice. Conclusion: Posttreatment with synthetic CRP effectively improves murine bacterial peritonitis via the activation of phagocytosis of Fc gamma RI-expressing Kupffer cells.