The preparation of a lipidic endotoxin affects its biological activities
The preparation of a lipidic endotoxin affects its biological activities
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DOI：
10.1248/bpb.31.1952
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发表时间：
2008-10-01
影响因子：
2
通讯作者：
Kawasaki, Kiyoshi
中科院分区：
文献类型：
--
作者：
Okemoto, Kazuo;Hanada, Kentaro;Kawasaki, Kiyoshi
细菌膜成分，如含鸟氨酸的脂质（OL）和脂多糖的脂质A部分，通过识别类TLR（TLR）4触发各种免疫反应。通常，这些脂质溶解在少量的水性或有机溶剂中，然后加入到培养基中以检查其生物活性。用溶于盐水中的OL或脂质A超声刺激的巨噬细胞释放白细胞介素-1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α）。相比之下，用OL或脂质A超声溶解在乙醇或二甲基亚砜（DMSO）中刺激的巨噬细胞分泌大量TNF-α，但分泌非常少的IL-1 β。这些结果综合起来表明，内毒素的制备方式影响其生物活性。此外，电子显微镜分析显示，在DMSO中超声处理空气干燥的OL或脂质A产生的颗粒比在盐水中产生的颗粒更大，这表明制备生物TLR 4配体的过程影响它们的物理状态，包括颗粒大小，并且物理状态可能是生物活性的重要决定因素
Bacterial membrane constituents, such as Ornithine-containing lipid (OL) and the lipid A portion of lipopolysaccharide, trigger various immune responses through recognition by Toil-like receptor (TLR) 4. Usually, these lipids are dissolved in a small amount of aqueous or organic solvent before being added to the culture medium for examination of their biological activities. Macrophages stimulated with OL or lipid A sonically dissolved in saline released both interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-a). In contrast, macrophages stimulated with OL or lipid A sonically dissolved in ethanol or dimethyl sulfoxide (DMSO) secreted much TNF-alpha, but very little IL-1 beta. These results, taken together, indicate that how an endotoxin is prepared affects its biological activities. In addition, electromicroscopic analysis revealed that sonication of air-dried OL or lipid A in DMSO produced larger particles than those produced in saline, suggesting that the process of preparing lipidic TLR4-ligands affects their physical state including particle size, and that the physical state might be an important determinant of biological activity