Perrin-Cocon Laure, Agaugué Sophie, Coutant Frédéric, Masurel Aurélie, Bezzine Sofiane, Lambeau Gérard, André Patrice, Lotteau Vincent
Institut Fédératif de Recherche 128, Institut National de la Santé et de la Recherche Médicale Unit 503, F-69365 Lyon Cedex 07, France.
Eur J Immunol. 2004 Aug;34(8):2293-302. doi: 10.1002/eji.200324797.
High level of phospholipase A(2) (PLA(2)) activity is found in serum and biological fluids during the acute-phase response (APR). Extracellular PLA(2) in fluids of patients with inflammatory diseases such as sepsis, acute pancreatitis or rheumatoid arthritis is also associated with propagation of inflammation. PLA(2) activity is involved in the release of both pro- and anti-inflammatory lipid mediators from phospholipids of cellular membranes or circulating lipoproteins. PLA(2) may thus generate signals that influence immune responses. Here, group III secretory PLA(2) were tested for their ability to promote generation of functionally mature human dendritic cells (DC). PLA(2) treatment of differentiating monocytes in the presence of granulocyte/macrophage colony-stimulating factor and IL-4 yielded cells with phenotypical and functional characteristics of mature DC. This maturation was dependent on the dose of PLA(2), and PLA(2)-generated DC stimulated IFN-gamma secretion by allogeneic T cells. The effects of PLA(2) on DC maturation was mainly dependent on enzyme activity and correlated with the activation of NF-kappaB, AP-1 and NFAT. The data suggest that transient increase in PLA(2) activity generates signals that promote transition of innate to adaptive immunity during the APR.
在急性期反应(APR)期间,血清和生物体液中发现高水平的磷脂酶A(2)(PLA(2))活性。在患有炎症性疾病(如败血症、急性胰腺炎或类风湿性关节炎)的患者的体液中,细胞外PLA(2)也与炎症的传播有关。PLA(2)活性参与从细胞膜磷脂或循环脂蛋白中释放促炎和抗炎脂质介质。因此,PLA(2)可能产生影响免疫反应的信号。在此,对III型分泌性PLA(2)促进功能成熟的人树突状细胞(DC)生成的能力进行了测试。在粒细胞/巨噬细胞集落刺激因子和IL-4存在的情况下,用PLA(2)处理分化中的单核细胞,产生具有成熟DC表型和功能特征的细胞。这种成熟取决于PLA(2)的剂量,并且PLA(2)生成的DC刺激同种异体T细胞分泌IFN-γ。PLA(2)对DC成熟的影响主要取决于酶活性,并且与NF-κB、AP-1和NFAT的激活相关。数据表明,PLA(2)活性的短暂增加产生促进APR期间先天免疫向适应性免疫转变的信号。