Endotoxin and nanobacteria in polycystic kidney disease

Endotoxin and nanobacteria in polycystic kidney disease
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DOI:
10.1046/j.1523-1755.2000.00096.x
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发表时间:
2000-06-01
影响因子:
19.6
通讯作者:
Darras, FS
Darras, FS
中科院分区:
医学1区
文献类型:
--
作者:
Hjelle, JT;Miller-Hjelle, MA;Darras, FS

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背景微生物曾被怀疑是多囊肾病(PKD)的病原体,但试图分离出活的微生物却失败了。细菌内毒素是PKD液体中最常报告的微生物产物。我们评估了13例PKD患者囊肿液、PKD患者尿液和对照组尿液中内毒素的潜在微生物来源。通过鉴别鲎变形细胞溶解物测定(dLAL)、属特异性抗脂多糖(LPS)抗体、纳米细菌单克隆抗体和汉赛巴尔通体超免疫血清(HS-Bh)来探测流体中的内毒素和纳米细菌(一种新细菌)。所选标本还通过透射电子显微镜(TEM)和纳米细菌培养方法进行了评估。LPS或其抗原代谢产物在超过75%的囊液中被发现。从13个PKD肾脏中的11个培养纳米细菌,通过TEM在8个肾脏中的8个中可视化,并且在所有13个PKD肾脏中进行免疫检测。通过免疫检测,在7名PKD男性中的7名、7名PKD女性中的1名、10名正常男性中的3名和10名正常女性中的1名的尿液中发现纳米细菌抗原。“血红纳米杆菌”呈dLAL阳性,并与抗衣原体LPS和HS-Bh发生交叉反应。一些囊肿液也阳性的大肠杆菌,脆弱拟杆菌和/或衣原体,和HS-Bh的LPS抗原,是一个病人的肝囊肿液。四环素和柠檬酸盐对纳米细菌的体外生长有抑制作用。纳米细菌或其抗原存在于PKD肾脏、肝脏和尿液中。鉴定候选微生物病原体是确定其对人类疾病的贡献(如果有的话)的第一步。
Background. Microbes have been suspected as provocateurs of polycystic kidney disease (PKD), but attempts to isolate viable organisms have failed. Bacterial endotoxin is the most often reported microbial product found in PKD fluids. We assessed potential microbial origins of endotoxin in cyst fluids from 13 PKD patients and urines of PKD and control individuals.Methods. Fluids were probed for endotoxin and nanobacteria, a new bacterium, by the differential Limulus Amebocyte Lysate ass ay (dLAL), genus-specific antilipopolysaccharide (LPS) antibodies, monoclonal antibodies to nanobacteria, and hyperimmune serum to Bartonella henselae (HS-Bh). Selected specimens were also assessed by transmission electron microscopy (TEM) and nanobacterial culture methods.Results. LPS or its antigenic metabolites were found in more than 75% of cyst fluids tested. Nanobacteria were cultured from 11 of 13 PKD kidneys, visualized in 8 of 8 kidneys by TEM, and immunodetected in all 13 PKD kidneys. By immunodetection, nanobacterial antigens were found in urine from 7 of 7 PKD males, 1 of 7 PKD females, 3 of 10 normal males, and 1 of 10 normal females. "Nanobacterium sanguineum" was dLAL positive and cross-reactive with antichlamydial LPS and HS-Bh. Some cyst fluids were also positive for LPS antigens from Escherichia coli, Bacteroides fragilis and/or Chlamydia, and HS-Bh, as were liver cyst fluids from one patient. Tetracycline and citrate inhibited nanobacterial growth in vitro.Conclusion. Nanobacteria or its antigens were present in PKD kidney, liver, and urine. The identification of candidate microbial pathogens is the first step in ascertaining their contribution, if any, to human disease.