A LIPOPOLYSACCHARIDE (LPS)-RESISTANT MUTANT ISOLATED FROM A MACROPHAGELIKE CELL-LINE, J774.1, EXHIBITS AN ALTERED ACTIVATED-MACROPHAGE PHENOTYPE IN RESPONSE TO LPS
A LIPOPOLYSACCHARIDE (LPS)-RESISTANT MUTANT ISOLATED FROM A MACROPHAGELIKE CELL-LINE, J774.1, EXHIBITS AN ALTERED ACTIVATED-MACROPHAGE PHENOTYPE IN RESPONSE TO LPS
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DOI：
10.1128/iai.59.6.2166-2174.1991
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发表时间：
1991-06-01
影响因子：
3.1
通讯作者：
AKAMATSU, Y
中科院分区：
文献类型：
--
作者：
AMANO, F;AKAMATSU, Y
从小鼠巨噬细胞样细胞株J774.1中分离到一株细菌脂多糖（LPS）抗性突变体。该突变体对LPS和脂质A表现出选择性抗性，抗性几乎是亲本的10(5)~ 10(6)倍；即使在每升1毫克的大肠杆菌O55:B5 LPS存在的情况下，它也能生长，而亲本在每毫升LPS低于10纳克的情况下也不能生长。接下来，我们检测了突变体在LPS处理下巨噬细胞各种功能的激活情况。这种抗脂多糖突变体分泌白细胞介素-1和肿瘤坏死因子的效率几乎与亲本一样高。突变细胞也瞬间由圆形变为扩散状；然而，他们后来又变圆了。突变细胞分泌较少的花生四烯酸响应LPS。这些结果还表明，这种LPS抗性突变体对LPS有反应，并表现出一些巨噬细胞功能的激活。然而，该突变体在LPS处理后并没有表现出O2生成或H2O2生成的增加。此外，用小鼠重组γ干扰素处理突变细胞部分能够纠正响应LPS时产生氧活性的缺陷，这表明这种缺陷可能是由于某些LPS信号通路造成的。这表明lps激活的巨噬细胞的O2代谢与细胞生长和活力下降之间存在一定的相关性。
A bacterial lipopolysaccharide (LPS)-resistant mutant was isolated from murine macrophagelike cell line J774.1. The mutant showed selective resistance to LPS and lipid A and was almost 10(5)- to 10(6)-fold more resistant than the parent; it grew even in the presence of 1 mg of Escherichia coli O55:B5 LPS per liter, whereas the parent did not grow with less than 10 ng of LPS per milliliter. We next examined the mutant for activation of various functions of macrophages on LPS treatment. This LPS-resistant mutant secreted interleukin-1 and tumor necrosis factor almost as effectively as the parent did. The mutant cells also changed transiently from a round to a spread form; however, they became round again afterwards. The mutant cells secreted less arachidonic acid in response to LPS. These results also suggest that this LPS-resistant mutant responds to LPS and shows activation of some macrophage functions. However, this mutant did not exhibit elevation of O2- generation or H2O2 generation after LPS treatment. Also, treatment of the mutant cells with murine recombinant gamma interferon was partly able to correct the defect in O2--generating activity in response to LPS, suggesting that this defect is probably due to some of the LPS signal pathways. This implies that there is some correlation between O2- metabolism in LPS-activated macrophages and decreases in cell growth and viability.