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Fas配体而非补体对于控制实验性金黄色葡萄球菌性眼内炎至关重要。

Fas ligand but not complement is critical for control of experimental Staphylococcus aureus Endophthalmitis.

作者信息

Engelbert Michael, Gilmore Michael S

机构信息

Departments of Microbiology and Immunology, and Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

出版信息

Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2479-86. doi: 10.1167/iovs.04-1139.

DOI:10.1167/iovs.04-1139

PMID:15980239

Abstract

PURPOSE

To determine the role of complement and Fas Ligand (FasL) in the host defense against Staphylococcus aureus endophthalmitis.

METHODS

C3-/-, FasL defective gld, and C57/BL6 (wild-type [WT]) mice were infected intravitreally with 500 and 5000 CFU S. aureus, and the course of infection was followed by determining the intraocular bacteria counts, retinal function by ERG, and morphologic damage and inflammation by histopathology and flow cytometry.

RESULTS

In WT eyes injected with 500 CFU, S. aureus grew to 1 x 10(7) CFU/mL by 24 hours, but was cleared by 96 hours. In the WT eyes injected with 5000 CFU, S. aureus grew to 2 x 10(9) CFU/mL by 72 hours, resulting in corneal perforation. C3-/- eyes injected with 500 CFU reached transiently higher levels than their WT counterparts (P < 0.001), but eventually followed a similar course. Bacterial counts in gld eyes infected with 500 CFU were similar to those in WT eyes infected with 5000 CFU. In WT and C3-/- eyes injected with 500 CFU, retinal function decreased only transiently and recovered to 66% in 72 hours. In WT eyes injected with 5000 CFU and gld eyes infected with 500 CFU, retinal function was completely lost by 24 hours. By 24 hours, WT and C3-/- eyes injected with 500 CFU were infiltrated with a similar number of granulocytes, but recruitment was significantly impaired in gld eyes (P < 0.005). Cell counts in WT and C3-/- eyes decreased thereafter without overt retinal disease. In eyes injected with 5000 CFU and gld eyes infected with 500 CFU, inflammatory cells completely filled the intraocular space by 48 hours. Retinal and uveal tissue was destroyed by that time.

CONCLUSIONS

The tipping point for a good versus a bad outcome in this murine model of endophthalmitis lies between 500 and 5000 CFU S. aureus. This point is identical in animals deficient in complement activation, suggesting that complement does not play a significant role in the ocular defense against intraocular bacteria. In contrast, FasL was found to be critical for clearance, since animals deficient in FasL signaling were unable to control infection with 500 CFU.

摘要

目的

确定补体和Fas配体（FasL）在宿主抵御金黄色葡萄球菌性眼内炎中的作用。

方法

将500和5000 CFU金黄色葡萄球菌玻璃体内注射到C3基因敲除小鼠、FasL缺陷型gld小鼠和C57/BL6（野生型[WT]）小鼠体内，通过测定眼内细菌数量、视网膜电图（ERG）检测视网膜功能以及组织病理学和流式细胞术检测形态学损伤和炎症反应来追踪感染过程。

结果

在注射500 CFU的WT小鼠眼中，金黄色葡萄球菌在24小时内增殖至1×l0⁷CFU/mL，但在96小时时被清除。在注射5000 CFU的WT小鼠眼中，金黄色葡萄球菌在72小时内增殖至2×l0⁹CFU/mL，导致角膜穿孔。注射500 CFU的C3基因敲除小鼠眼内细菌数量暂时高于WT小鼠（P<0.001），但最终感染过程相似。感染500 CFU的gld小鼠眼内细菌数量与感染5000 CFU的WT小鼠相似。在注射500 CFU的WT和C3基因敲除小鼠眼中，视网膜功能仅暂时下降，72小时内恢复至66%。在注射5000 CFU的WT小鼠眼和感染500 CFU的gld小鼠眼中，视网膜功能在24小时内完全丧失。在注射500 CFU的WT和C3基因敲除小鼠眼中，24小时时浸润的粒细胞数量相似，但gld小鼠眼中的粒细胞募集明显受损（P<0.005）。此后，WT和C3基因敲除小鼠眼中的细胞数量减少，未出现明显的视网膜疾病。在注射5000 CFU的小鼠眼和感染500 CFU的gld小鼠眼中，48小时时炎症细胞完全充满眼内空间。此时视网膜和葡萄膜组织被破坏。