Mizuno Masashi, Ito Yasuhiko, Hepburn Natalie, Mizuno Tomohiro, Noda Yukihiro, Yuzawa Yukio, Harris Claire L, Morgan B Paul, Matsuo Seiichi
Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
J Immunol. 2009 Jul 15;183(2):1403-12. doi: 10.4049/jimmunol.0804245. Epub 2009 Jun 24.
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 C3b 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 C3b 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.
真菌性腹膜炎是腹膜透析患者的一种重要并发症；持续性或复发性腹膜炎均可加重腹膜损伤。即使在真菌性腹膜炎患者拔除腹膜透析导管后，腹膜纤维化仍可进展并演变为包裹性腹膜硬化。目前尚不清楚为何真菌感染在这些方面比细菌感染更严重。酵母聚糖是酵母的一种细胞壁成分，能强烈激活补体系统。在本研究中，我们在机械刮擦诱导的大鼠腹膜损伤模型中比较了酵母聚糖和细菌脂多糖对腹膜炎症的影响。腹腔注射酵母聚糖可导致明显增强的腹膜炎，在第5天出现大量细胞浸润以及补体激活产物C3b和膜攻击复合物的沉积，而注射脂多糖或溶剂则无此现象。在注射酵母聚糖并于第18天或第36天处死的大鼠中，腹膜炎症持续存在，伴有ED-1阳性细胞积聚、少量C3b和膜攻击复合物沉积、纤维蛋白原渗出以及腹膜下组织毛细血管增生。在腹膜刮擦后每天注射酵母聚糖，持续5天，会出现更严重的腹膜炎症，伴有腹膜增厚、炎性细胞积聚和补体沉积。用眼镜蛇毒因子预处理进行全身补体抑制或腹腔注射重组补体调节因子Crry-Ig进行局部抑制，均可减轻酵母聚糖处理大鼠的腹膜炎症。我们的结果表明，酵母成分通过在腹腔内引起补体激活来加剧受损腹膜的炎症。因此，局部抗补体治疗可能在腹膜真菌感染期间保护腹膜免受损伤。
