Entzian P, Pawelek W, Lindner B, Schlaak M, Zabel P, Müller-Quernheim J
Medizinische Klinik, Forschungszentrum Borstel.
Pneumologie. 1998 Dec;52(12):674-9.
Search for beryllium (Be) in tissues or urine in suspected beryllium disease is often disappointing due to inferior sensitivity of the methods employed. We evaluated the clinical use of laser microprobe mass spectrometry (LAMMS) for measurement of Be and detected the metal to a minimum concentration of 1 microM. We then investigated the biological relevance of this concentration. We looked at the alveolar macrophages in 7 patients subsequent to an incubation period of 24 h as well as peripheral blood mononuclear cells (PBMNC) and various cell lines with and without addition of beryllium sulfate (BeSO4). We also investigated skin biopsies of two patients 28 days after intracutaneous injections of BeSO4 (beryllium skin testing) and alveolar macrophages of A/J mice at various time intervals after a beryllium sensitisation protocol and a single intratracheal injection of BeSO4 (maximum interval: 15 weeks). Be was not defectable in native patient alveolar macrophages (AM), but in 6 of 7 cases after coincubation with BeSO4. There was no significant Be signal in any analysed PBMNC sample or cell line--even after coincubation with Be--or in the skin probes. Murine AM, however, had incorporated significant amounts of Be, which were detectable until the end of the experiments 15 weeks later. We conclude that concentrations of Be in acute disease (here, inoculation of Be in mice) exceed 1 microM and are thus detectable by LAMMS. On the other hand, concentrations in chronic processes (in this cosar, skin testing) are below the detection limits of LAMMS. Further results suggest compartmentalisation of the immune processes induced by Be because the alveolar macrophages were able to incorporate Be while PBMNC were not and because AM--at least in the animal experiments--seem to store Be intracellularly.
由于所采用方法的灵敏度较低，在疑似铍病患者的组织或尿液中寻找铍（Be）的结果往往不尽人意。我们评估了激光微探针质谱法（LAMMS）在测量铍方面的临床应用，并检测到该金属的最低浓度为1微摩尔。然后，我们研究了这一浓度的生物学相关性。我们观察了7名患者在24小时潜伏期后的肺泡巨噬细胞，以及外周血单核细胞（PBMNC）和添加或不添加硫酸铍（BeSO4）的各种细胞系。我们还研究了两名患者在皮内注射BeSO4（铍皮肤试验）28天后的皮肤活检样本，以及A/J小鼠在经过铍致敏方案和单次气管内注射BeSO4（最长间隔：15周）后的不同时间间隔的肺泡巨噬细胞。在天然患者肺泡巨噬细胞（AM）中未检测到铍，但在7例中的6例与BeSO4共同孵育后检测到了铍。在任何分析的PBMNC样本或细胞系中，即使与铍共同孵育后，或在皮肤样本中，均未检测到明显的铍信号。然而，小鼠AM中摄取了大量的铍，直到15周后的实验结束时仍可检测到。我们得出结论，急性疾病（此处为小鼠接种铍）中的铍浓度超过1微摩尔，因此可通过LAMMS检测到。另一方面，慢性过程（在此例中为皮肤试验）中的浓度低于LAMMS的检测限。进一步的结果表明，铍诱导的免疫过程存在区室化，因为肺泡巨噬细胞能够摄取铍，而PBMNC则不能，并且至少在动物实验中，AM似乎在细胞内储存铍。
