附红细胞体感染诱发补体异常活化导致溶血的研究

Excessive activation of complement induced by porcine eperythrozoon infection causes hemolysis

目的附红细胞体(Eperythrozoon,EP)病是人兽共患性血液传染病,可以引发溶血、出血、血栓形成、流产等,其主要的致病机制不清,本研究应用源于猪的EP感染研究其致病机制。方法收集EP感染养殖生猪27头和13例汉族饲养人员,对照组为无EP感染的同种猪26头和健康汉族人末梢血20份。ELISA和流式细胞检测猪和人感染EP后血清补体C3及其降解产物、补体调节蛋白CD55、CD59、补体膜攻击复合物(C5b-9)沉积及细胞因子在猪冠状动脉内皮中的表达。结果EP感染后猪和人血清C3降解产物C3a升高有统计学意义(P<0.05),猪红细胞CD55和CD59阴性比例显著增加具有显著的统计学意义(P<0.01),红细胞膜和猪血管内皮沉积大量C5b-9,同时血管内膜中细胞因子产生增加具有统计学意义(P<0.05)。结论EP感染诱发补体异常活化导致红细胞及血管内皮损伤,引发溶血、出血、血栓形成等。

Eperythrozoon(hemoplasma or hemotrophic mycoplasma,EP)infection is a type of hematologic infectious zoonosis.This infection can cause hemolysis,thrombosis,bleeding and diminished immunity,but the main pathogenesis mechanisms are unknown.EP infection was diagnosed primarily through light microscopy and confirmed with PCR amplification of the EP 16S rRNA gene in 13 pig farmers and 27 domesticated pigs.Samples from 26 healthy pigs and 20 healthy pig farmers were used as controls.Peripheral blood from humans and pigs,and coronary artery samples from pigs were collected.The erythrocytes,white blood cells,serum and coronary artery endothelia were isolated.Flow cytometry and enzyme-linked immuno-sorbent assay were used to quantify the complement elements in the peripheral blood and the production of IL-1α,IL-2 and IFN-γin the isolated protein from coronary artery endothelia.Tests indicated that EP infection caused erythrocytic deformation and also induced C5b-9 deposition on red blood cells in humans and pigs(P<0.01).In addition,the infection decreased circulating C3 and increased C3a in both humans and pigs(P<0.01).Accumulated pro-inflammatory cytokines IL-1α,IL-2 and IFN-γ(P<0.01)in were observed porcine coronary artery endothelia.EP infection in both pigs and humans caused EP attachment to red blood cell membranes,and simultaneously induced excessive complement activation and non-specific inflammation,thereby causing hemolysis,micro-thrombosis and bleeding.