GRAM-POSITIVE CELL-WALLS STIMULATE SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 BY HUMAN MONOCYTES
GRAM-POSITIVE CELL-WALLS STIMULATE SYNTHESIS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-6 BY HUMAN MONOCYTES
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DOI：
10.1128/iai.62.7.2715-2721.1994
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发表时间：
1994-07-01
影响因子：
3.1
通讯作者：
TOMASZ, A
中科院分区：
文献类型：
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作者：
HEUMANN, D;BARRAS, C;TOMASZ, A
纯化的细胞壁，代表了各种各样的磷壁酸和肽聚糖的结构，从八个不同的革兰氏阳性细菌物种诱导生产的肿瘤坏死因子α（TNF-α）和白细胞介素-6的人单核细胞在10%的血浆或血清的存在下。当浓度高于100 ng至1 μ g细胞壁/ml时，开始产生大量细胞因子，最大产量需要10至100 μ g细胞壁材料/ml。在不存在血浆的情况下，细胞壁制剂的烟碱诱导能力降低至少一个数量级。在90 ℃下加热30 min可使血清衍生辅因子失活，这表明活性与蛋白质相关。另一方面，用低丙种球蛋白血症血浆替代正常血浆、补体失活（56 ℃）以及单核细胞上CD 14受体的单克隆抗体MY 4阻断并不能抑制由整个细胞壁诱导的TNF-α的产生。在多粘菌素B存在的情况下，细胞壁也刺激TNF-α的产生，并且来自C3 He/HeJ小鼠的脂多糖不敏感细胞系的巨噬细胞在受到细胞壁刺激时也产生这种细胞因子。通过酶促方法从相同壁制备物制备的肽聚糖和可溶性聚糖-磷壁酸组分均表现出从单核细胞中血清依赖性诱导TNF-α，而茎肽和二acharide肽仅具有差的活性（如果有的话）。细胞壁可能参与革兰氏阳性菌诱导的败血性休克。
Purified cell walls representing a wide variety in teichoic acid and peptidoglycan structure prepared from eight different gram-positive bacterial species induced the production of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 from human monocytes in the presence of 10% plasma or serum. Significant amounts of cytokines began to be produced at concentrations above 100 ng to 1 mu g of cell waifs per ml, with maximal production requiring 10 to 100 mu g of cell wall material per ml. In the absence of plasma, the cytokine-inducing capacity of cell wall preparations was lower by at least an order of magnitude. The serum-derived cofactor was inactivated by heating at 90 degrees C for 30 min, suggesting that the activity is associated with a protein, bn the other hand, replacement of normal with hypogammaglobulinemic plasma, inactivation of complement (at 56 degrees C), and blockade by the monoclonal antibody MY4 of the CD14 receptors on monocytes did not inhibit the production of TNF-alpha induced by whole cell walls. Cell walls also stimulated production of TNF-alpha in the presence of polymyxin B, and macrophages derived from the lipopolysaccharide-insensitive cell line of C3He/HeJ mice also produced this cytokine when stimulated by cell walls. Both peptidoglycan and the soluble glycan-teichoic acid component prepared by an enzymatic method from the same wall preparation exhibited a serum-dependent induction of TNF-alpha from monocytes, while stem peptides and disacharride peptides had only poor, if any, activity. Cell walls may contribute to the septic shock induced by gram-positive bacteria.