Schutyser E, Struyf S, Wuyts A, Put W, Geboes K, Grillet B, Opdenakker G, Van Damme J
Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
Eur J Immunol. 2001 Dec;31(12):3755-62. doi: 10.1002/1521-4141(200112)31:12<3755::aid-immu3755>3.0.co;2-o.
Chemokines are mediators of innate and acquired immunity. CCL18, also designated pulmonary and activation-regulated chemokine (PARC), dendritic cell-derived CC chemokine-1 (DC-CK1), alternative macrophage activation-associated CC chemokine-1 (AMAC-1) and macrophage inflammatory protein-4 (MIP-4), was for the first time isolated from peripheral blood mononuclear cells (PBMC) and biochemically characterized. We found that CCL18/PARC protein is spontaneously secreted by PBMC and is selectively induced in PBMC by staphylococcal enterotoxins (SEA, SEB) and IL-4, but not by IFN-gamma and the CXCL8/IL-8 inducers lipopolysaccharide (LPS) or Concanavalin A. Human fibroblasts, chondrocytes and endothelial cells did not produce CCL18/PARC in response to inflammatory mediators such as measles virus, double-stranded RNA, LPS or IL-1beta, whereas up to 150 ng/ml of CCL2/MCP-1 was induced under these conditions. In synovial fluids from septic and rheumatoid arthritis patients, fourfold-enhanced CCL18/PARC levels (150 ng/ml) were detected compared to those in crystal-induced arthritis and osteoarthritis. In septic arthritis, the synovial levels of CCL18/PARC were fivefold higher than those of CXCL8/IL-8. Immunochemistry revealed CD68(+) monocytes/macrophages as the main CCL18/PARC-producing cell type in both PBMC and arthritic synovial tissue. In addition, CD1a(+) blood dendritic cells expressed CCL18/PARC. These findings suggest that monocytic cells respond to Gram-positive bacterial infection by the production of CCL18/PARC in the synovial cavity.
趋化因子是先天性和获得性免疫的介质。CCL18，也被称为肺和激活调节趋化因子（PARC）、树突状细胞衍生的CC趋化因子-1（DC-CK1）、替代性巨噬细胞激活相关CC趋化因子-1（AMAC-1）和巨噬细胞炎性蛋白-4（MIP-4），首次从外周血单核细胞（PBMC）中分离出来并进行了生化特性鉴定。我们发现CCL18/PARC蛋白由PBMC自发分泌，并在PBMC中被葡萄球菌肠毒素（SEA、SEB）和IL-4选择性诱导，但不被IFN-γ以及CXCL8/IL-8诱导剂脂多糖（LPS）或伴刀豆球蛋白A诱导。人成纤维细胞、软骨细胞和内皮细胞在受到炎症介质如麻疹病毒、双链RNA、LPS或IL-1β刺激时不产生CCL18/PARC，而在这些条件下可诱导产生高达150 ng/ml的CCL2/MCP-1。在脓毒性关节炎和类风湿性关节炎患者的滑液中，与晶体诱导性关节炎和骨关节炎相比，检测到CCL18/PARC水平提高了四倍（150 ng/ml）。在脓毒性关节炎中，CCL18/PARC的滑液水平比CXCL8/IL-8高五倍。免疫化学显示CD68(+)单核细胞/巨噬细胞是PBMC和关节炎滑膜组织中产生CCL18/PARC的主要细胞类型。此外，CD1a(+)血液树突状细胞表达CCL18/PARC。这些发现表明单核细胞通过在滑膜腔中产生CCL18/PARC来应对革兰氏阳性细菌感染。
