Zhang X, Morrison D C
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City 66160.
J Exp Med. 1993 Feb 1;177(2):511-6. doi: 10.1084/jem.177.2.511.
Preculture of thioglycollate-elicited C3HeB/FeJ mouse peritoneal macrophages in vitro with subthreshold stimulatory concentrations of lipopolysaccharide (LPS) can induce hyporesponsiveness (desensitization) to both tumor necrosis factor alpha (TNF-alpha) and nitric oxide (NO) production when these cells are subsequently stimulated with 100 ng/ml of LPS. We have established, however, that the primary dose of LPS required for inducing downregulation of NO production is significantly lower than that required for inducing downregulation of TNF-alpha production. Further, when LPS-pretreated macrophages become refractory to subsequent LPS stimulation for NO production, the secondary LPS-stimulated TNF-alpha production is markedly enhanced, and vice versa. These results indicate that LPS-induced TNF-alpha and NO production by macrophages are differentially regulated, and that the observed desensitization process may not reflect a state in which macrophages are totally refractory to subsequent LPS stimulation. Rather, our data suggest that LPS-pretreated macrophages become selectively primed for differential responses to LPS. The LPS-induced selective priming effects are not restricted to LPS stimulation, but extend as well to stimuli such as zymosan, Staphylococcus aureus, and heat-killed Listeria monocytogenes.
用亚阈值刺激浓度的脂多糖（LPS）在体外对巯基乙酸诱导的C3HeB/FeJ小鼠腹腔巨噬细胞进行预培养，当这些细胞随后用100 ng/ml的LPS刺激时，可诱导其对肿瘤坏死因子α（TNF-α）和一氧化氮（NO）产生反应低下（脱敏）。然而，我们已经确定，诱导NO产生下调所需的LPS初始剂量显著低于诱导TNF-α产生下调所需的剂量。此外，当LPS预处理的巨噬细胞对随后的LPS刺激产生NO变得不应答时，二次LPS刺激的TNF-α产生会显著增强，反之亦然。这些结果表明，LPS诱导的巨噬细胞产生TNF-α和NO受到不同的调节，并且观察到的脱敏过程可能并不反映巨噬细胞对随后的LPS刺激完全不应答的状态。相反，我们的数据表明，LPS预处理的巨噬细胞会选择性地被致敏，以对LPS产生不同反应。LPS诱导的选择性致敏作用不仅限于LPS刺激，还扩展到诸如酵母聚糖、金黄色葡萄球菌和热灭活的单核细胞增生李斯特菌等刺激物。
