Seyler I, Appel M, Devissaguet J P, Legrand P, Barratt G
URA-CNRS 1218, Faculty of Pharmacy, Chatenay-Malabry, France.
Int J Immunopharmacol. 1996 Jun-Jul;18(6-7):385-92. doi: 10.1016/s0192-0561(96)00041-0.
The present study evaluates the ability of a new drug carrier: nanocapsules of poly(D,L-lactide) containing muramyldipeptide-L-alanyl-cholesterol (MTP-Chol NC) to induce activation of mouse macrophage cell lines. MTP-Chol NC stimulated nitric oxide (NO) expression and tumor necrosis factor-alpha (TNF-alpha) production, these are two important mediators of macrophage-mediated cytotoxicity. The encapsulated form was more effective than free muramyldipeptide, at low immunomodulator concentrations. The dose-response curves were completely different for NO and TNF-alpha, implying different regulatory mechanisms. In RAW 264.7 cells, the addition of anti-TNF-alpha antibodies during the activation period did not affect the level of nitrite induced by MTP-Chol Nc and lipopolysaccharide. Therefore, autocrine stimulation by TNF-alpha did not contribute to NO production. On the other hand, the presence of an NO synthase inhibitor led to an increase in TNF-alpha secretion. In J774.A1 cells, which were activated by MTP-Chol NC and interferon-gamma, TNF-alpha production seemed to act as a second messenger. Thus, under certain conditions, NO can play a role in modulating the cytotoxic activities of mouse macrophages.
含有胞壁酰二肽-L-丙氨酰-胆固醇的聚（D，L-丙交酯）纳米胶囊（MTP-Chol NC）诱导小鼠巨噬细胞系激活的能力。MTP-Chol NC刺激了一氧化氮（NO）表达和肿瘤坏死因子-α（TNF-α）产生，这两者是巨噬细胞介导的细胞毒性的两个重要介质。在低免疫调节剂浓度下，包封形式比游离胞壁酰二肽更有效。NO和TNF-α的剂量反应曲线完全不同，这意味着不同的调节机制。在RAW 264.7细胞中，在激活期添加抗TNF-α抗体并不影响MTP-Chol Nc和脂多糖诱导的亚硝酸盐水平。因此，TNF-α的自分泌刺激对NO产生没有作用。另一方面，NO合酶抑制剂的存在导致TNF-α分泌增加。在由MTP-Chol NC和干扰素-γ激活的J774.A1细胞中，TNF-α产生似乎充当第二信使。因此，在某些条件下，NO可在调节小鼠巨噬细胞的细胞毒性活性中发挥作用。
