Synovial tissue macrophage as a source of the chemotactic cytokine IL-8.
Synovial tissue macrophage as a source of the chemotactic cytokine IL-8.
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DOI：
10.4049/jimmunol.147.7.2187
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发表时间：
1991-10
影响因子：
4.4
通讯作者：
A. Koch;S. Kunkel;J. Burrows;H. Evanoff;G. K. Haines;R. Pope;R. Strieter
中科院分区：
文献类型：
--
作者：
A. Koch;S. Kunkel;J. Burrows;H. Evanoff;G. K. Haines;R. Pope;R. Strieter
关节炎患者的滑膜微环境的细胞可以募集中性粒细胞（PMN）和淋巴细胞进入滑液，以及淋巴细胞进入滑膜组织。我们已经调查了生产的趋化细胞因子IL-8通过使用血清，滑液，滑膜组织，巨噬细胞和成纤维细胞分离的滑膜组织从75关节炎患者。类风湿（RA）患者滑液中的IL-8水平（平均值± SE，14.37 ± 5.8 ng/ml）高于骨关节炎患者滑液（0.135 ± 17 ng/ml）（p <0.05）或其他关节炎患者滑液（5.52 ± 5.11 ng/ml）。RA血清中IL-8为8.44 +/- 2.33 ng/ml，而正常血清中检测不到。RA血清和滑液中IL-8水平呈强正相关（r = 0.96，p <0.05）。此外，RA滑液中PMN的趋化活性抑制40 +/-5%后，与IL-8的中和多克隆抗体孵育。滑膜组织成纤维细胞仅释放少量的组成型IL-8，但可以通过用IL-1 β、TNF-α或LPS刺激来诱导产生IL-8。相反，与正常PBMC或肺泡巨噬细胞不同，从RA滑膜组织分离的巨噬细胞组成型表达IL-8 mRNA和抗原性IL-8。RA滑膜巨噬细胞IL-8的表达没有增加与LPS，TNF-α，或IL-1 β孵育。滑膜组织的免疫组织化学分析表明，RA巨噬细胞比骨关节炎巨噬细胞与抗IL-8反应的百分比更大。巨噬细胞是IL-8免疫定位的主要细胞，而不到5%的滑膜组织成纤维细胞对免疫定位的IL-8呈阳性。这些结果表明，巨噬细胞源性IL-8可能在RA相关滑膜炎症中PMN的募集中发挥重要作用。
Cells of the synovial microenvironment may recruit neutrophils (PMN) and lymphocytes into synovial fluid, as well as lymphocytes into the synovial tissues, of arthritic patients. We have investigated the production of the chemotactic cytokine IL-8 by using sera, synovial fluid, synovial tissue, and macrophages and fibroblasts isolated from synovial tissues from 75 arthritic patients. IL-8 levels were higher in synovial fluid from rheumatoid (RA) patients (mean +/- SE, 14.37 +/- 5.8 ng/ml), compared with synovial fluid from osteoarthritis patients (0.135 +/- 17 ng/ml) (p less than 0.05) or from patients with other arthritides (5.52 +/- 5.11 ng/ml). IL-8 from RA sera was 8.44 +/- 2.33 ng/ml, compared with nondetectable levels found in normal sera. IL-8 levels from RA sera and synovial fluid were strongly positively correlated (r = 0.96, p less than 0.05). Moreover, RA synovial fluid chemotactic activity for PMN in these fluids was inhibited 40 +/- 5% upon incubation with neutralizing polyclonal antibody to IL-8. Synovial tissue fibroblasts released only small amounts of constitutive IL-8 but could be induced to produce IL-8 by stimulation with either IL-1 beta, TNF-alpha, or LPS. In contrast, unlike normal PBMC or alveolar macrophages, macrophages isolated from RA synovial tissue constitutively expressed both IL-8 mRNA and antigenic IL-8. RA synovial macrophage IL-8 expression was not augmented by incubation with either LPS, TNF-alpha, or IL-1 beta. Immunohistochemical analysis of synovial tissue showed that a greater percentage of RA macrophages than osteoarthritis macrophages reacted with anti-IL-8. Whereas macrophages were the predominant cell for immunolocalization of IL-8, less than 5% of synovial tissue fibroblasts were positive for immunolocalized IL-8. These results suggest that macrophage-derived IL-8 may play an important role in the recruitment of PMN in synovial inflammation associated with RA.