Folkard S G, Westwick J, Millar A B
University of Bristol, Dept of Hospital Medicine, Southmead Hospital, Westbury on Trym, UK.
Eur Respir J. 1997 Sep;10(9):2097-104. doi: 10.1183/09031936.97.10092097.
The aim of this study was to determine the relative production of chemokines interleukin-8 (IL-8), regulated on activation, normal T-cell expressed and secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) by intrinsic and extrinsic asthmatics. Nine intrinsic asthmatics, 10 extrinsic asthmatics, five nonatopic and five atopic controls underwent bronchoalveolar lavage (BAL). Total BAL cells were cultured in the presence or absence of lipopolysaccharide. Chemokines were measured in BAL cell supernatants and in cell-free bronchoalveolar lavage fluid (BALF) by enzyme-linked immunoabsorbent assay (ELISA). BAL cell cytospins were stained immunohistochemically for chemokines. BAL cells from asthmatics produced more IL-8 than controls (statistically significant for extrinsic asthma). RANTES was elevated in the BAL cell supernatants of four out of nine intrinsic asthmatics as compared to nonatopic controls (not statistically significant). RANTES levels in the BAL cell supernatants of extrinsic asthmatics were all low. MCP-1 production by BAL cells was similar in all groups. Immunostaining of BAL cell cytospins showed the macrophage to be the predominant positive-staining cell type and correlated well with supernatant data. Measurement of chemokines in BALF showed significantly elevated IL-8 in intrinsic asthma compared to nonatopic controls, but no increase in extrinsic asthmatics relative to atopic control RANTES was elevated in three out of nine BALFs from intrinsic asthmatics compared with nonatopic controls (not statistically significant). MCP-1 was not elevated above control levels in BALF of either asthma group. These results suggest an up-regulation in the production of interleukin-8 and regulated on activation, normal T-cell expressed and secreted, but not monocyte chemotactic protein-1 (MCP-1), by macrophages in the bronchoalveolar lavage of asthmatic subjects. In addition, the data suggest that regulated on activation, normal T-cell, expressed and secreted, may be differentially produced by macrophages in atopic and nonatopic asthma.
本研究的目的是确定内源性和外源性哮喘患者趋化因子白细胞介素-8（IL-8）、活化调节正常T细胞表达和分泌因子（RANTES）以及单核细胞趋化蛋白-1（MCP-1）的相对产生量。9名内源性哮喘患者、10名外源性哮喘患者、5名非特应性对照者和5名特应性对照者接受了支气管肺泡灌洗（BAL）。将总的BAL细胞在有或无脂多糖的情况下进行培养。通过酶联免疫吸附测定（ELISA）法检测BAL细胞上清液和无细胞支气管肺泡灌洗液（BALF）中的趋化因子。对BAL细胞涂片进行趋化因子免疫组织化学染色。哮喘患者的BAL细胞产生的IL-8比对照者多（外源性哮喘差异有统计学意义）。与非特应性对照者相比，9名内源性哮喘患者中有4名的BAL细胞上清液中RANTES升高（差异无统计学意义）。外源性哮喘患者的BAL细胞上清液中RANTES水平均较低。所有组中BAL细胞产生MCP-1的情况相似。BAL细胞涂片的免疫染色显示巨噬细胞是主要的阳性染色细胞类型，且与上清液数据相关性良好。BALF中趋化因子的检测显示，与非特应性对照者相比，内源性哮喘患者的IL-8显著升高，但外源性哮喘患者相对于特应性对照者无升高。与非特应性对照者相比，9份内源性哮喘患者的BALF中有3份的RANTES升高（差异无统计学意义）。两组哮喘患者的BALF中MCP-1均未升高至对照水平以上。这些结果表明，哮喘患者支气管肺泡灌洗中的巨噬细胞上调了白细胞介素-8以及活化调节正常T细胞表达和分泌因子的产生，但未上调单核细胞趋化蛋白-1（MCP-1）的产生。此外，数据表明，活化调节正常T细胞表达和分泌因子可能在特应性和非特应性哮喘中由巨噬细胞差异产生。
