Brunelleschi S, Guidotto S, Tonso E, Viano I, Fantozzi R
Department of Medical Sciences, University of Turin, Novara, Italy.
Neuropeptides. 1996 Jun;30(3):249-60. doi: 10.1016/s0143-4179(96)90071-2.
As previously reported, alveolar macrophages (AMs) from ovalbumin-sensitized guinea pigs present an enhanced responsiveness to tachykinins but not to N-formylmethionyl-leucyl-phenylalanine (fMLP). We have investigated the biochemical mechanisms underlying this varied responsiveness to tachykinins. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) induced a larger superoxide anion (O2-) production in AMs from sensitized guinea pigs, as did tachykinins. Pretreatment of AMs with pertussis toxin abolished tachykinin-evoked respiratory burst, had no effect on PMA-evoked O2- production and strongly inhibited fMLP-evoked one, with no appreciable variation between control or sensitized AMs. Staurosporine and its derivative cgp 41251, significantly decreased PMA- and tachykinin-evoked O2- production in both populations, being more potent in control AMs, but exerted little effects against fMLP. Pretreatment of AMs with PMA significantly inhibited fMLP-, PMA- and tachykinin-evoked O2- production in both control and sensitized AMs. fMLP, substance P (SP), neurokinin A (NKA) and the NK2 agonist [beta-Ala8]-NKA(4-10) dose-dependently increased [3H] phorbol 12, 13 dibutyrate (PDBu) binding to control and sensitized AMs. While fMLP exerted similar effects in both populations, dose-response curves for SP1 NKA and the NK2 receptor agonist were shifted leftwards (1, 4 and 3 orders of magnitude, respectively) in sensitized AMs. These results indicate a possible PKC involvement in the enhanced responsiveness to tachykinins in actively sensitized AMs.
如先前报道，来自卵清蛋白致敏豚鼠的肺泡巨噬细胞（AMs）对速激肽呈现出增强的反应性，但对N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）则无此反应。我们研究了对速激肽这种不同反应性背后的生化机制。蛋白激酶C（PKC）激活剂佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导致敏豚鼠AMs产生更大的超氧阴离子（O2-），速激肽也有此作用。用百日咳毒素预处理AMs可消除速激肽诱发的呼吸爆发，对PMA诱发的O2-产生无影响，并强烈抑制fMLP诱发的O2-产生，对照或致敏AMs之间无明显差异。星形孢菌素及其衍生物cgp 41251显著降低了两组细胞中PMA和速激肽诱发的O2-产生，对对照AMs作用更强，但对fMLP几乎无作用。用PMA预处理AMs可显著抑制对照和致敏AMs中fMLP、PMA和速激肽诱发的O2-产生。fMLP、P物质（SP）、神经激肽A（NKA）和NK2激动剂[β-丙氨酸8]-NKA（4-10）剂量依赖性地增加[3H]佛波酯12,13-二丁酸酯（PDBu）与对照和致敏AMs的结合。虽然fMLP在两组细胞中作用相似，但致敏AMs中SP、NKA和NK2受体激动剂的剂量反应曲线向左移动（分别为1、4和3个数量级）。这些结果表明PKC可能参与了主动致敏AMs对速激肽增强的反应性。
