背景:肝硬化腹水(PCA)患者易患自发性细菌性腹膜炎(SBP),其发病率和死亡率增加。由于来自PCA的腹膜巨噬细胞(PMú)的某些宿主防御方面发生了变化,因此本研究检查了与受体介导的吞噬作用相关的因素。
方法:研究了12种PCA。从这些患者取出的腹水(AF)样品中分离出PM。甘露糖受体(MR)特异性配体的摄取,异硫氰酸荧光素甘露糖基化牛血清白蛋白(FITC-man-BSA),由患者和对照组,人类单核细胞系,在IL-4治疗前后进行测量。在IL-4治疗前后测量患者对FITC标记的酵母颗粒的吞噬作用。使用分光光度计获得荧光值。在PCA和对照的血液样本中分析了MRC1基因,健康的捐献者,使用标准聚合酶链反应(PCR)技术。
结果:58.3%的患者报告了过去的SBP发作。每位患者分析的平均AF体积为1.3L。细胞产量中的PMV比率为53.73%(SD18.1)。患者的平均摄取吸光度为0.0841(SD0.077),而对照组为0.338(SD0.34),P=0.023。IL-4治疗后,患者的吸光度增加到0.297(SD0.28)PM损失(配对样本t检验P=0.018),至0.532(对照组为SD0.398(独立样本t检验P=0.053)。IL-4治疗前患者的平均吞噬吸光度为0.1250(SD0.032),而治疗后为0.2300(SD0.104)(P=0.026)。与所有对照的阳性结果相比,所有PCA样品中MRC1基因的PCR分析均为阴性。
结论:由于IL-4治疗后吞噬作用降低和MR摄取增强,因此治疗前MR下调是合理的。MRC1的阴性PCR结果可能提示异常,但这有待进一步的澄清。这些改变的宿主防御发现与感染病理生理学有关,它们与PCA中SBP敏感性的相关性值得验证。
BACKGROUND: Patients with cirrhotic ascites (PCA) are susceptible to spontaneous bacterial peritonitis (SBP) which has increased morbidity and mortality. Since some host defense aspects of peritoneal macrophages (PMф) from PCA are altered this study examined factors related to receptor-mediated phagocytosis.
METHODS: Twelve PCA were studied. PMɸ were isolated from ascitic fluid (AF) samples removed from these patients. Uptake of mannose receptor (MR)-specific ligand, fluorescein isothiocyanate-mannosylated-bovine serum albumin (FITC-man-BSA), by patients\' PMɸ and controls, a human monocytic cell line, was measured pre- and post-IL-4 treatment. Phagocytosis of FITC-labeled yeast particles by patients\' PMɸ was measured pre- and post-IL-4 treatment. Fluorescence values were obtained using a spectrofuorometer. MRC1 gene was analyzed in blood samples from PCA and controls, healthy donors, using standard polymerase chain reaction (PCR) technique.
RESULTS: Past SBP episode(s) were reported in 58.3% of patients. Mean AF volume analyzed per patient was 1.3L. PMɸ ratio in cell yield was 53.73% (SD 18.1). Mean uptake absorbance of patients\' PMф was 0.0841 (SD 0.077) compared to 0.338 (SD 0.34) of controls, P = 0.023. Following IL-4 treatment absorbance increased to 0.297 (SD 0.28) in patients\' PMф (P = 0.018 on paired sample t-test), and to 0.532 (SD 0.398 in controls (P = 0.053 on independent sample t-test). Mean phagocytosis absorbance of patients\' PMф was 0.1250 (SD 0.032) before IL-4 treatment compared to 0.2300 (SD 0.104) after (P = 0.026). PCR analysis for MRC1 gene was negative in all PCA samples compared to positive results in all controls.
CONCLUSIONS: Since decreased phagocytosis and MR uptake were enhanced post-IL-4 treatment MR downregulation pre-treatment is plausible. Negative PCR results for MRC1 might suggest an anomaly, but this awaits further ellucidation. These altered host defense findings are relevant to infection pathophysiology, and their relevance to SBP susceptibility in PCA is worth verifying.