Lipopolysaccharide and phorbol 12-myristate 13-acetate both impair monocyte differentiation, relating cellular function to virus susceptibility
Lipopolysaccharide and phorbol 12-myristate 13-acetate both impair monocyte differentiation, relating cellular function to virus susceptibility
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DOI：
10.1046/j.1365-2567.2001.01266.x
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发表时间：
2001-08-01
期刊：
影响因子：
6.4
通讯作者：
McCullough, KC
中科院分区：
文献类型：
--
作者：
Basta, S;Knoetig, S;McCullough, KC
脂多糖（LPS）和肉豆蔻酸酯（PMA）均通过典型的表型调节和某些吞噬细胞相关过程阻碍单核细胞向巨噬细胞的分化。猪单核细胞标志物SWC1的下调和巨噬细胞标志物SWC9的上调被延缓，但未被抑制，分化相关的p53和髓过氧化物酶的下调也是如此。尽管巨噬细胞分化明显受损，但并非所有细胞功能都同样易受影响。两种药物均抑制吞噬作用，但不抑制低密度脂蛋白受体相关的内吞作用。只有LPS抑制酒石酸抗性酸性磷酸酶的上调。相比之下，液泡酸化速率的增加更容易受到PMA的影响。某些内体/溶酶体酶（酯酶、核苷酸酶、过氧化物酶和组织蛋白酶）的活性普遍被LPS和PMA增强。这与通过诱导抗病毒状态检测到的自噬体活性形成对比。破坏自噬体和溶酶体（蛋氨酸- o -甲酯），而不是溶酶体（甘酰基-l-苯丙氨酸）逆转lps诱导的病毒复制抑制，而不影响pma诱导的抗病毒效果。因此，当使用原代血单核细胞时，PMA在抑制单核细胞向巨噬细胞分化方面与LPS相似，但并非所有途径都同样敏感。分析表明，在单核细胞分化过程中调节的途径在一定程度上是独立的。此外，单核细胞的某些功能对病毒感染的结果更为重要，自噬体活动尤其有利于细胞存活。
Both lipopolysaccharide (LPS) and phorbol 12-myristate 13-acetate (PMA) impeded monocyte to macrophage differentiation with respect to typical phenotypic modulation and certain phagocyte-related processes. The down-regulation of the porcine monocyte marker SWC1, and up-regulation of the SWC9 macrophage marker were retarded, but not inhibited, as was the differentiation-associated down-regulation of p53 and myeloperoxidase. Despite this clear impairment of macrophage differentiation, not all cellular functions were equally susceptible. Both agents inhibited phagocytosis, but not low-density lipoprotein receptor-associated endocytosis. Only LPS inhibited tartrate-resistant acid phosphatase up-regulation. In contrast, increase of vacuolar acidification rates was more susceptible to PMA. The activity of certain endosomal/lysosomal enzymes - esterase, nucleotidase, peroxidase and cathepsins - was generally enhanced by both LPS and PMA. This contrasted with autophagosomal activity, detected through the induction of an antiviral state. Disruption of autophagosomes and lysosomes (methionine-O-methyl ester), but not lysosomes alone (glycyl-l-phenylalanine) reversed LPS-induced inhibition of virus replication, without influencing the PMA-induced antiviral effect. Thus, PMA is similar to LPS in inhibiting monocyte to macrophage differentiation, when primary blood monocytes are employed, but not all pathways are equally susceptible. The analyses demonstrate that the pathways modulated during monocyte differentiation function somewhat independently. Moreover, certain functions of monocytic cells are more important with respect to the outcome of virus infection, with autophagosomal activities in particular favouring cell survival.