Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro.
Endogenous norepinephrine regulates tumor necrosis factor-alpha production from macrophages in vitro.
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DOI：
10.4049/jimmunol.152.6.3024
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发表时间：
1994-03
影响因子：
4.4
通讯作者：
R. Spengler;S. Chensue;D. Giacherio;Nicole Blenk;S. Kunkel
中科院分区：
文献类型：
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作者：
R. Spengler;S. Chensue;D. Giacherio;Nicole Blenk;S. Kunkel
去甲肾上腺素在神经元外蓄积的证据已被证明发生在巨噬细胞(M Phi)，但这一系统的生理作用仍不明确。我们评估了小鼠腹膜M phi对肾上腺素能拮抗剂的反应。我们还确定了非特异性肾上腺素能激动剂去甲肾上腺素的M Phi相关池的生理作用。我们研究了α-肾上腺素能和β-肾上腺素能受体在内毒素诱导的肿瘤坏死因子-α产生中的结构性参与。CFA诱导的M PHIs与内毒素(1微克/毫升)孵育，加入或不加入肾上腺素能激动剂和/或拮抗剂。虽然刺激α-肾上腺素能受体增加了肿瘤坏死因子的产生和基因表达，但β-肾上腺素能受体减少了它。有趣的是，当肾上腺素能拮抗剂和内毒素单独加入M Phi时，它们产生的反应与其合适的激动剂所产生的反应相反，这表明内源性去甲肾上腺素在M Phi中起作用。因此，尽管α2-肾上腺素能拮抗剂减弱了肿瘤坏死因子的产生，但β-肾上腺素能拮抗剂以浓度依赖的方式增强了肿瘤坏死因子的表达。用高效液相色谱法测定M phi中有去甲肾上腺素和肾上腺素的含量，内毒素刺激使其含量显著降低。M PHIs也与内毒素孵育或单独培养，洗涤，12h后用内毒素攻击。当给予第二次内毒素刺激时，M PHI对α2-肾上腺素能激动剂的反应增强，对α2-肾上腺素能拮抗剂的反应降低。因此，M Phi相关的去甲肾上腺素似乎以自分泌的方式调节内毒素诱导的肿瘤坏死因子的产生。
Evidence for the extraneuronal accumulation of norepinephrine has been demonstrated to occur in macrophage (M phi), yet the physiologic role of this system remains undefined. We have assessed the response of murine peritoneal M phi to adrenergic antagonists. We have also defined a physiologic role of a M phi-associated pool of the nonspecific adrenergic agonist norepinephrine. We investigated the constitutive involvement of alpha-adrenergic and beta-adrenergic receptors in LPS-induced TNF-alpha production. CFA-elicited M phis were incubated with LPS (1 microgram/ml) in the presence or absence of adrenergic agonists and/or antagonists. Although stimulation of alpha-adrenergic receptors increased TNF production and gene expression, beta-adrenergic receptors decreased it. Interestingly, when adrenergic antagonists along with LPS alone were added to M phi, they generated the response opposite to that produced by their suitable agonist, suggesting a role for endogenous norepinephrine in M phi. Thus, although alpha 2-adrenergic antagonists attenuated TNF production, beta-adrenergic antagonists augmented TNF expression in a concentration-dependent manner. Norepinephrine and epinephrine were found in M phi as determined by HPLC and LPS stimulation induced a significant decrease in their content. M phis were also incubated with LPS or medium only, washed, and then challenged 12 h later with LPS. When given a second LPS stimulation, M phis were found to have an increased response to alpha 2-adrenergic agonists and decreased response to alpha 2-adrenergic antagonists. Therefore, M phi-associated norepinephrine appears to regulate LPS-induced TNF production in an autocrine fashion.