Mege J L, Sanguedolce M V, Jacob T, Bongrand P, Capo C, Myssiakine E B, Barot-Ciorbaru R
Laboratoire d'Immunologie, Hôpital de Sainte-Marguerite, Marseille, France.
Eur J Immunol. 1993 Jul;23(7):1582-7. doi: 10.1002/eji.1830230728.
Nocardia lysozyme digest (NLD) and Nocardia water-soluble mitogen (NWSM) are two fractions derived from Nocardia opaca. In this report, we demonstrated that both fractions elicited significant secretion of tumor necrosis factor-alpha (TNF-alpha) in human monocytes. Supernatants from monocytes stimulated with NWSM and low concentrations of NLD displayed a cytotoxic activity against TNF-alpha-sensitive L929 cells, but supernatants from monocytes stimulated with high concentrations of NLD failed to lyse L929 cells. This latter phenomenon might be related to the secretion of an inactive form of TNF-alpha or the release of an inhibitor of TNF-alpha cytotoxic activity. Since it is well established that protein kinase C (PKC) plays a major role in the signaling of several monocyte activators, we investigated the putative role of PKC in cytokine synthesis induced by NLD and NWSM fractions. TNF-alpha secretion in response to both Nocardia fractions was inhibited by sphingosine, staurosporine and calphostin C, known PKC inhibitors, as well as by a PKC depletion procedure. In addition, NLD and NWSM induced a transient increase in [3H]phorbol dibutyrate binding, which assessed the activation of PKC. The data suggest the involvement of PKC in the signaling of NLD and NWSM fractions leading to the synthesis and the secretion of TNF-alpha by human monocytes.
诺卡氏菌溶菌酶消化物（NLD）和诺卡氏菌水溶性促细胞分裂剂（NWSM）是从不透明诺卡氏菌中提取的两个组分。在本报告中，我们证明这两种组分均可诱导人单核细胞大量分泌肿瘤坏死因子-α（TNF-α）。用NWSM和低浓度NLD刺激的单核细胞培养上清液对TNF-α敏感的L929细胞具有细胞毒性活性，但用高浓度NLD刺激的单核细胞培养上清液未能裂解L929细胞。后一种现象可能与无活性形式的TNF-α的分泌或TNF-α细胞毒性活性抑制剂的释放有关。由于蛋白激酶C（PKC）在几种单核细胞激活剂的信号传导中起主要作用已得到充分证实，我们研究了PKC在NLD和NWSM组分诱导的细胞因子合成中的假定作用。已知的PKC抑制剂鞘氨醇、星形孢菌素和钙磷蛋白C以及PKC耗竭程序均抑制了对两种诺卡氏菌组分的反应中TNF-α的分泌。此外，NLD和NWSM诱导[3H]佛波醇二丁酸酯结合短暂增加，这评估了PKC的激活。数据表明PKC参与了NLD和NWSM组分的信号传导，导致人单核细胞合成和分泌TNF-α。
