Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Nephrol Dial Transplant. 2011 Jun;26(6):1821-30. doi: 10.1093/ndt/gfq683. Epub 2010 Nov 22.
The peritoneal cavity is isolated from the outside and is usually a sterile environment. Patients on peritoneal dialysis (PD) have PD fluid (PDF) infused into the peritoneal cavity. We previously showed that unregulated complement activation could contribute to the development of peritoneal inflammation in yeast peritonitis in PD therapy. In that situation, suppression of local complement activation is essential to protect the host from further injury. The membrane complement regulators (CRegs), Crry, CD55 and CD59, are expressed in the rat peritoneum, especially along the mesothelial cell layer.
We investigated CRegs' functional roles in the peritoneal cavity using blocking mAb against each CReg and complement activation in different PDFs.
Blockade of any single CReg did not cause spontaneous peritoneal injury in rat. Combined blockade of Crry and CD59 induced focal peritoneal tissue injury and heavy accumulation of inflammatory cells with peritoneal edema at 24 h. Deposits of C3 and C5b-9 were found on the peritoneal surface after combined blocking of Crry and CD59. Systemic complement depletion by cobra venom factor abrogated these inflammatory changes. When combined blockade of Crry and CD59 was performed with PDF of different pH and glucose concentration in rats, the peritoneal injuries were enhanced with lower pH and higher glucose concentration. These results were confirmed by in vitro experiments using primary rat mesothelial cell culture.
Rat CRegs, Crry and CD59, specifically collaborate to control complement activation in rat peritoneum. During PD, impairment of CReg might contribute to the development of severe peritoneal inflammation.
腹腔与外界隔离，通常是无菌环境。接受腹膜透析（peritoneal dialysis，PD）的患者将 PD 液（peritoneal dialysis fluid，PDF）注入腹腔。我们之前的研究表明，补体激活失调可能导致 PD 治疗中酵母性腹膜炎时的腹膜炎症发展。在这种情况下，抑制局部补体激活对于保护宿主免受进一步损伤至关重要。膜补体调节蛋白（membrane complement regulators，CRegs），如 Crry、CD55 和 CD59，在大鼠腹膜中表达，特别是沿间皮细胞层表达。
我们使用针对每种 CReg 的阻断 mAb 研究了 CRegs 在腹膜腔中的功能作用，以及在不同 PDF 中的补体激活情况。
阻断任何单一 CReg 都不会导致大鼠自发性腹膜损伤。Crry 和 CD59 的联合阻断导致 24 小时时出现局灶性腹膜组织损伤和炎症细胞大量积聚伴腹膜水肿。Crry 和 CD59 的联合阻断后，在腹膜表面发现 C3 和 C5b-9 的沉积。蛇毒因子（cobra venom factor）引起的系统性补体耗竭消除了这些炎症变化。当在大鼠的不同 pH 值和葡萄糖浓度的 PDF 中进行 Crry 和 CD59 的联合阻断时，随着 pH 值降低和葡萄糖浓度升高，腹膜损伤加剧。这些结果通过使用原代大鼠间皮细胞培养的体外实验得到了证实。
大鼠 CRegs，Crry 和 CD59，特异性地协同控制大鼠腹膜中的补体激活。在 PD 期间，CRegs 的损伤可能导致严重的腹膜炎症发展。
