Ignatowski T A, Spengler R N
Department of Pathology, SUNY at Buffalo, School of Medicine and Biomedical Sciences 14214, USA.
J Neuroimmunol. 1995 Aug;61(1):61-70. doi: 10.1016/0165-5728(95)00074-c.
Catecholamines and prostaglandins are among the many diverse mediators which participate in an interactive communication between the nervous and immune systems. We have examined the response of murine peritoneal macrophages (M luminal diameter) to prostaglandin-E2 (PGE2) and the beta-adrenergic agonist isoproterenol. In the present study we found a relationship between the response elicited by PGE2 and a beta-adrenergic agonist, which in a fashion similar to the response of PGE2 on M luminal diameters suppresses lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production. It has been established that exposure of M luminal diameters to PGE2 desensitizes the suppressive function of PGE2. In this study, prior exposure of M luminal diameters to a beta-adrenergic agonist and the effects on subsequent beta-adrenergic responses, as well as the relationship to PGE2 sensitivity was determined. Complete Freund's adjuvant-elicited M luminal diameters were incubated with or without either a beta-adrenergic agonist or antagonist. All groups of cells were then extensively washed, followed by incubation with LPS (100 ng/ml) with or without graded concentrations of PGE2 or the beta-adrenergic agonist isoproterenol. Supernatants were collected to determine TNF concentrations by a fibroblast cytolytic assay, and Northern blot analysis was used to determine changes in the regulation of TNF mRNA accumulation. Both isoproterenol and PGE2 inhibited LPS-stimulated TNF release and TNF mRNA accumulation. We have established M luminal diameters regulation of sensitivity to isoproterenol-induced suppression of TNF production. The isoproterenol concentration-effect curve was shifted to the right after pre-exposure of M luminal diameter to the beta-agonist, suggesting a desensitized beta-adrenergic receptor population. Further studies demonstrated that M luminal diameters pre-exposed to the beta-adrenergic antagonist, ICI 118.551, washed, and then challenged with LPS show an increased sensitivity for isoproterenol-induced suppression of TNF production. In addition, a decreased sensitivity of M luminal diameters to exogenous PGE2 was observed during the desensitization to the beta-adrenergic agonist. Although concomitant addition of isoproterenol increased PGE2-induced suppression of LPS-stimulated TNF production, M luminal diameter pre-exposed to isoproterenol (10(-6) M) demonstrated a decreased sensitivity for PGE2-induced suppression of LPS-stimulated TNF production and TNF mRNA accumulation. Our results show that the effects observed after acute administration of a mediator may be different when M luminal diameters have been previously exposed to that or other mediators. These investigations support a role for mediators released from the nervous system to regulate the release of a cytokine needed to maintain inflammatory responses.
儿茶酚胺和前列腺素是参与神经和免疫系统间交互通讯的众多不同介质中的一部分。我们研究了小鼠腹腔巨噬细胞（M管腔直径）对前列腺素E2（PGE2）和β-肾上腺素能激动剂异丙肾上腺素的反应。在本研究中，我们发现PGE2和β-肾上腺素能激动剂引发的反应之间存在一种关系，其以类似于PGE2对M管腔直径的反应方式抑制脂多糖（LPS）诱导的肿瘤坏死因子（TNF）产生。已经确定M管腔直径暴露于PGE2会使PGE2的抑制功能脱敏。在本研究中，确定了M管腔直径预先暴露于β-肾上腺素能激动剂及其对后续β-肾上腺素能反应的影响，以及与PGE2敏感性的关系。将完全弗氏佐剂诱导的M管腔直径与β-肾上腺素能激动剂或拮抗剂一起或不一起孵育。然后将所有细胞组充分洗涤，接着与LPS（100 ng/ml）一起孵育，同时加入或不加入分级浓度的PGE2或β-肾上腺素能激动剂异丙肾上腺素。收集上清液通过成纤维细胞溶细胞测定法测定TNF浓度，并使用Northern印迹分析来确定TNF mRNA积累调节的变化。异丙肾上腺素和PGE2均抑制LPS刺激的TNF释放和TNF mRNA积累。我们确定了M管腔直径对异丙肾上腺素诱导的TNF产生抑制的敏感性调节。在M管腔直径预先暴露于β-激动剂后，异丙肾上腺素浓度-效应曲线向右移动，表明β-肾上腺素能受体群体脱敏。进一步的研究表明，预先暴露于β-肾上腺素能拮抗剂ICI 118.551、洗涤后再用LPS刺激的M管腔直径对异丙肾上腺素诱导的TNF产生抑制表现出增加的敏感性。此外，在对β-肾上腺素能激动剂脱敏期间观察到M管腔直径对外源性PGE2的敏感性降低。尽管同时加入异丙肾上腺素会增加PGE2诱导的对LPS刺激的TNF产生的抑制，但预先暴露于异丙肾上腺素（10^(-6) M）的M管腔直径对PGE2诱导的对LPS刺激的TNF产生和TNF mRNA积累的抑制表现出降低的敏感性。我们的结果表明，当M管腔直径先前已暴露于该介质或其他介质时，急性给予一种介质后观察到的效应可能会有所不同。这些研究支持神经系统释放的介质在调节维持炎症反应所需的细胞因子释放中起作用。
