Haschek W M, Gumprecht L A, Smith G, Tumbleson M E, Constable P D
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, Illinois, USA.
Environ Health Perspect. 2001 May;109 Suppl 2(Suppl 2):251-7. doi: 10.1289/ehp.01109s2251.
Fumonisin toxicosis in swine was named porcine pulmonary edema (PPE) after outbreaks of a fatal disease in pigs fed Fusarium verticillioides (F. moniliforme)-contaminated corn screenings from the 1989 corn crop in Iowa, Illinois, and Georgia. Pigs that died had severe pulmonary edema, which has not been identified in other species after exposure to fumonisins. The disease has been reproduced experimentally by feeding of naturally contaminated corn, F. verticillioides culture material, and by intravenous administration of fumonisin B1 (FB1). Hepatic lesions consisting of apoptosis, necrosis, and hepatocyte proliferation also are observed. As in other species, alterations in clinical pathology reflect hepatic injury as well as elevated serum cholesterol concentration. In chronic studies, esophageal plaques, hyperplastic hepatic nodules, and right ventricular hypertrophy were found. In pigs, as in other species, fumonisin alters sphingolipid biosynthesis, with the greatest alterations in sphingosine and sphinganine concentrations in kidney, liver, lung, and heart. Our recent studies on fumonisin toxicosis in pigs have focused on immune effects and the pathogenesis of pulmonary edema. The specific immune system was not affected; however, FB1 inhibited phagocytosis and sphingolipid biosynthesis in pulmonary macrophages. Fumonisin induced an accumulation of membranous material in pulmonary capillary endothelial cells; this change appears specific to this cell type and to swine. In short-term cardiovascular studies, fumonisin decreased left ventricular dP/dt(max) (an index of cardiac contractility), mean systemic arterial pressure, heart rate, and cardiac output, and increased mean pulmonary artery pressure and pulmonary artery wedge pressure. These changes are compatible with the inhibition of L-type calcium channels by increased sphingosine and/or sphinganine concentration. Therefore, fumonisin-induced pulmonary edema in swine appears to result from acute left-sided heart failure mediated by altered sphingolipid biosynthesis.
猪的伏马菌素中毒在爱荷华州、伊利诺伊州和佐治亚州爆发致命疾病后被命名为猪肺水肿（PPE），这些猪食用了受轮枝镰孢菌（串珠镰刀菌）污染的1989年玉米作物的玉米筛屑。死亡的猪有严重的肺水肿，在其他物种接触伏马菌素后未发现这种情况。通过喂食天然污染的玉米、轮枝镰孢菌培养物以及静脉注射伏马菌素B1（FB1），已在实验中再现了这种疾病。还观察到由细胞凋亡、坏死和肝细胞增殖组成的肝脏病变。与其他物种一样，临床病理学变化反映了肝损伤以及血清胆固醇浓度升高。在慢性研究中，发现了食管斑块、增生性肝结节和右心室肥大。在猪中，与其他物种一样，伏马菌素会改变鞘脂生物合成，肾脏、肝脏、肺和心脏中鞘氨醇和二氢鞘氨醇浓度的变化最大。我们最近对猪伏马菌素中毒的研究集中在免疫效应和肺水肿的发病机制上。特异性免疫系统未受影响；然而，FB1抑制了肺巨噬细胞中的吞噬作用和鞘脂生物合成。伏马菌素诱导肺毛细血管内皮细胞中膜性物质的积累；这种变化似乎特定于这种细胞类型和猪。在短期心血管研究中，伏马菌素降低了左心室dP/dt（max）（心脏收缩力指标）、平均体动脉压、心率和心输出量，并增加了平均肺动脉压和肺动脉楔压。这些变化与鞘氨醇和/或二氢鞘氨醇浓度增加对L型钙通道的抑制作用一致。因此，伏马菌素诱导的猪肺水肿似乎是由鞘脂生物合成改变介导的急性左心衰竭引起的。
