Zymosan, but Not Lipopolysaccharide, Triggers Severe and Progressive Peritoneal Injury Accompanied by Complement Activation in a Rat Peritonitis Model
Zymosan, but Not Lipopolysaccharide, Triggers Severe and Progressive Peritoneal Injury Accompanied by Complement Activation in a Rat Peritonitis Model
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DOI：
10.4049/jimmunol.0804245
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发表时间：
2009-07-15
影响因子：
4.4
通讯作者：
Matsuo, Sefchi
中科院分区：
文献类型：
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作者：
Mizuno, Masashi;Ito, Yasuhiko;Matsuo, Sefchi
真菌性腹膜炎是腹膜透析患者的重要并发症；持续或复发性腹膜炎可能会加重腹膜损伤。即使真菌性腹膜炎患者的腹膜透析导管被拔除，腹膜纤维化也可能进展并演变成包膜腹膜硬化。目前还不清楚为什么真菌感染在这些方面比细菌感染更严重。酵母聚糖是酵母的细胞壁成分，可强烈激活补体系统。在本研究中，我们比较了酵母聚糖和细菌脂多糖对机械刮擦引起的大鼠腹膜损伤模型中腹膜炎症的影响。腹膜内给予酵母聚糖，而不是LPS或媒介物，在第5天引起明显增强的腹膜炎，细胞大量浸润和补体激活产物Cab和膜攻击复合物沉积。在给予酵母聚糖并在第18或36天处死的大鼠中，腹膜炎症持续存在，ED-1阳性细胞积聚，Cab和膜攻击复合物少量沉积，纤维蛋白原渗出，腹膜下毛细血管增殖组织。当腹膜刮擦后每天给予酵母聚糖5天时，腹膜炎症更加严重，腹膜增厚、炎症细胞积聚和补体沉积。通过眼镜蛇毒因子预处理或腹腔注射局部抑制来抑制全身补体。给予重组补体调节剂 Crry-Ig 可以减轻酵母聚糖治疗大鼠的腹膜炎症。我们的结果表明，酵母成分通过引起腹膜腔内的补体激活来加剧受损腹膜的炎症。因此，局部抗补体治疗可以防止腹膜真菌感染期间的腹膜损伤。免疫学杂志，2009，183：1403-14.12。
Fungal peritonitis is an important complication in peritoneal dialysis patients; either continuous or recurrent peritonitis may enhance peritoneal damage. Even when the peritoneal dialysis catheter is removed in patients with fungal peritonitis, peritoneal fibrosis can progress and evolve into encapsular peritoneal sclerosis. It is unclear why fungal infections are worse than bacterial in these respects. Zymosan is a cell wall component of yeast that strongly activates the complement system. In this study, we compared the effects of zymosan and bacterial LPS on peritoneal inflammation in a rat peritoneal injury model induced by mechanical scraping. Intraperitoneal administration of zymosan, but not LPS or vehicle, caused markedly enhanced peritonitis with massive infiltration of cells and deposition of complement activation products Cab and membrane attack complex on day 5. In rats administered zymosan and sacrificed on days 18 or 36, peritoneal inflammation persisted with accumulation of ED-1-positive cells, small deposits of Cab and membrane attack complex, exudation of fibrinogen, and capillary proliferation in subperitoneal tissues. When zymosan was administered daily for 5 days after peritoneal scrape, there was even greater peritoneal inflammation with peritoneal thickening, inflammatory cell accumulation, and complement deposition. Inhibition of systemic complement by pretreatment with cobra venom factor or local inhibition by i.p. administration of the recombinant complement regulator Crry-Ig reduced peritoneal inflammation in zymosan-treated rats. Our results show that yeast components augment inflammation in the injured peritoneum by causing complement activation within the peritoneal cavity. Local anticomplement therapy may therefore protect from peritoneal damage during fungal infection of the peritoneum. The Journal of Immunology, 2009, 183: 1403-14.12.