Koch A E, Kunkel S L, Shah M R, Hosaka S, Halloran M M, Haines G K, Burdick M D, Pope R M, Strieter R M
Department of Medicine, Northwestern University Medical School, Chicago, IL 60611, USA.
J Immunol. 1995 Oct 1;155(7):3660-6.
Leukocyte recruitment is critical in the inflammation seen in rheumatoid arthritis (RA). To determine whether the chemokine growth-related gene product alpha (gro alpha) plays a role in this process, we examined synovial tissue (ST), synovial fluid (SF), and plasma samples from 102 patients with arthritis. RA SF contained more antigenic gro alpha (mean 5.3 +/- 1.9 ng/ml) than did SFs from either osteoarthritis (OA) or other forms of arthritis (mean 0.1 ng/ml) (p < 0.05). RA plasma contained more gro alpha (mean 4.3 +/- 1.8 ng/ml) than normal plasma (mean 0.1 ng/ml) (p < 0.05). RA ST fibroblasts (1.2 x 10(5)/cells/mI RPMI 1640/24 h) produced antigenic gro alpha (mean 0.2 +/- 0.1 ng/ml), and this production was increased significantly upon incubation with TNF-alpha (mean 1.3 +/- 0.3 ng/ml) or IL-1 beta (mean 2.3 +/- 0.6 ng/ml) (p < 0.05). Cells from RA SF also produced gro alpha: neutrophils (PMNs) (10(7) cells/mI/24 h) produced 3.7 +/- 0.7 ng/ml. RA SF mononuclear cells produced gro alpha, particularly upon incubation with LPS or PHA. Immunoreactive ST gro alpha was found in greater numbers of RA compared with either OA or normal lining cells, as well as in RA compared with OA subsynovial macrophages (p < 0.05). IL-8 accounted for a mean of 36% of the RA SF chemotactic activity for PMNs, while epithelial neutrophil-activating peptide-78 accounted for 34%, and gro alpha for 28%, of this activity. Combined neutralization of all three chemokines in RA SFs resulted in a mean decrease of 50% of the chemotactic activity for PMNs present in the RA SFs. These results indicate that gro alpha plays an important role in the ingress of PMNs into the RA joint.
白细胞募集在类风湿关节炎（RA）的炎症反应中至关重要。为了确定趋化因子生长相关基因产物α（groα）是否在此过程中发挥作用，我们检测了102例关节炎患者的滑膜组织（ST）、滑液（SF）和血浆样本。RA的SF中抗原性groα含量（平均5.3±1.9 ng/ml）高于骨关节炎（OA）或其他形式关节炎的SF（平均0.1 ng/ml）（p<0.05）。RA血浆中groα含量（平均4.3±1.8 ng/ml）高于正常血浆（平均0.1 ng/ml）（p<0.05）。RA的ST成纤维细胞（1.2×10⁵/细胞/ml RPMI 1640/24小时）产生抗原性groα（平均0.2±0.1 ng/ml），与肿瘤坏死因子-α（TNF-α）（平均1.3±0.3 ng/ml）或白细胞介素-1β（IL-1β）（平均2.3±0.6 ng/ml）孵育后，这种产生显著增加（p<0.05）。RA SF中的细胞也产生groα：中性粒细胞（PMN）（10⁷细胞/ml/24小时）产生3.7±0.7 ng/ml。RA SF单核细胞产生groα，特别是与脂多糖（LPS）或植物血凝素（PHA）孵育后。与OA或正常衬里细胞相比，在RA中发现免疫反应性ST groα的数量更多，与OA滑膜下巨噬细胞相比，在RA中也是如此（p<0.05）。IL-8平均占RA SF对PMN趋化活性的36%，而上皮中性粒细胞激活肽-78占该活性的34%，groα占28%。对RA SF中所有三种趋化因子进行联合中和导致RA SF中PMN趋化活性平均降低50%。这些结果表明groα在PMN进入RA关节的过程中起重要作用。
