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小鼠体内经氯化铁处理的内毒素生物活性评估

Evaluation of biologic activity of ferric chloride-treated endotoxin in mice.

作者信息

Galley C B, Walker R I, Ledney G D, Gambrill M R

出版信息

Exp Hematol. 1975 Jun;3(3):197-204.

PMID:239854
Abstract

Endotoxin (lipopolysaccharide, LPS) treated with ferric chloride was tested for its potential as a non-toxic agent for enhancement of non-specific host resistance. A 1 mg dose of untreated endotoxin, injected i.p. into mice, resulted in 100 per cent mortality, whereas the same amount of chemically-treated endotoxin resulted in less than 35 per cent lethality. The radio-protective potential of the treated endotoxin was similar to that of untreated endotoxin, as 70 per cent of each group of mice tested with either substance survived a dose of 850 rad x-ray. Irradiated mice, challenged 8 days after 850 rad x-irradiation, died when injected with 25 mug of either untreated or treated endotoxin. Antibiotic decontamination of the intestinal tract of host animals reduced the possibility of toxicity from endogenous endotoxin after challenge. This treatment resulted in 100 per cent survival from a 25 mug challenge at 8 days post-irradiation. The ferric chloride-treated proved to be a more effective B-lymphocyte mitogen. At a dose of 100 mug, treated endotoxin resulted in a 50 per cent greater mitogenic stimulation of B-lymphocytes as compared with that found after exposure to untreated endotoxin. Several lines of evidence support the contention that tolerance to untreated endotoxin was induced by repeated injections of either endotoxin preparation 1) 100 per cent of all endotoxin-tolerant mice survived a 1 mg challenge dose of untreated endotoxin, 2) there was a reduced mitotic response of splenic B-lymphocytes after re-exposure with untreated endotoxin as compared with that observed for cells derived from saline-treated mice, and 3) all antibiotic decontaminated mice engrafted with spleen cells from mice made tolerant to either endotoxin preparation survive graft-versus-host disease. In conclusion, based on survival data from normal mice, ferric chloride-treated endotoxin is safer to use than normal endotoxin. Also, treated endotoxin can elicit biologic responses similar in magnitude to those found after injection of mice with untreated endotoxin.

摘要

用氯化铁处理的内毒素(脂多糖,LPS)被测试其作为增强非特异性宿主抵抗力的无毒剂的潜力。1毫克未处理的内毒素腹腔注射到小鼠体内,导致100%的死亡率,而相同量的化学处理内毒素导致的致死率低于35%。处理后的内毒素的辐射防护潜力与未处理的内毒素相似,因为用这两种物质测试的每组小鼠中有70%在接受850拉德X射线照射后存活。在850拉德X射线照射8天后受到攻击的受辐照小鼠,注射25微克未处理或处理过的内毒素后死亡。对宿主动物肠道进行抗生素去污可降低攻击后内源性内毒素产生毒性的可能性。这种处理导致在辐照后8天接受25微克攻击的小鼠100%存活。经氯化铁处理的内毒素被证明是一种更有效的B淋巴细胞有丝分裂原。在100微克的剂量下,与未处理的内毒素相比,处理后的内毒素对B淋巴细胞的有丝分裂刺激作用增强了50%。几条证据支持这样的观点,即通过重复注射任何一种内毒素制剂可诱导对未处理内毒素的耐受性:1)所有对内毒素耐受的小鼠中有100%在接受1毫克未处理内毒素的攻击剂量后存活;2)与盐水处理小鼠来源的细胞相比,再次接触未处理内毒素后脾B淋巴细胞的有丝分裂反应降低;3)所有用来自对内毒素制剂耐受的小鼠的脾细胞移植的抗生素去污小鼠均存活移植物抗宿主病。总之,根据正常小鼠的存活数据,氯化铁处理的内毒素比正常内毒素使用起来更安全。此外,处理后的内毒素能引发与给小鼠注射未处理内毒素后相似程度的生物学反应。

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