Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia

Pneumolysin-induced complement depletion during experimental pneumococcal bacteremia
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DOI:
10.1128/iai.69.6.3569-3575.2001
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发表时间:
2001-06-01
影响因子:
3.1
通讯作者:
Gentry-Nielsen, MJ
Gentry-Nielsen, MJ
中科院分区:
医学2区
文献类型:
--
作者:
Alcantara, RB;Preheim, LC;Gentry-Nielsen, MJ

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为了量化肺炎链球菌菌血症期间肺炎球菌溶血素对补体的消耗,用表达不同形式肺炎链球菌溶血素的三种肺炎链球菌同基因突变株之一静脉内感染肝硬化大鼠和对照大鼠。结果指标包括从血流中清除微生物、感染期间 50% 血清溶血补体 (CH50) 活性和补体 C3 水平的变化以及感染后 18 小时的血清调理能力。感染前后,肝硬化大鼠的 CH50 和 C3 水平均显着低于对照大鼠,但是,初始补体水平并不能预测感染 18 小时后的细菌负荷,18 小时内 CH50 和 C3 水平的变化与感染后 18 小时血流中的 H+C+ 数量相关,但与 H+C- 或 PLY- 微生物数量无关。 C3 对肺炎链球菌的调理活性显着低于 H+C+ 感染对照大鼠的血清。这些研究表明,在补体浓度有限的情况下,肺炎球菌表达的肺炎球菌溶血素对血清补体水平具有显着的负面影响,并降低血清调理活性。
To quantify complement depletion by pneumolysin during Streptococcus pneumoniae bacteremia, cirrhotic and control rats were infected intravenously with one of three isogenic mutant strains of S. pneumoniae expressing different forms of pneumolysin. Outcome measures included clearance of the organisms from the bloodstream, alterations in 50% serum hemolytic complement (CH50) activity and complement C3 levels during infection, and serum opsonic capacity at 18 h postinfection. Cirrhotic rats had significantly lower CH50 and C3 levels than control rats, both before and after infection, However, initial complement levels did not predict bacterial load after 18 h of infection, Changes in CH50 and C3 levels over the 18-h period correlated with numbers of H+C+ but not H+C- or PLY- organisms in the bloodstream at 18 h postinfection, The sera of cirrhotic rats infected with the H+C+ strain had significantly decreased levels of C3 and showed significantly lower opsonizing activity for S. pneumoniae than sera from H+C+-infected control rats. These studies suggest that under limiting concentrations of complement, the expression of pneumolysin by pneumococci has a significant, negative effect on serum complement levels and reduces serum opsonic activity.