Volin M V, Shah M R, Tokuhira M, Haines G K, Woods J M, Koch A E
Northwestern University Medical School, Lakeside Division, Chicago, Illinois, 60611, USA.
Clin Immunol Immunopathol. 1998 Oct;89(1):44-53. doi: 10.1006/clin.1998.4590.
Rheumatoid arthritis (RA) is characterized by recruitment of leukocytes from the vasculature into inflamed synovial tissue (ST) and synovial fluid (SF), which depends, in part, upon the continued maintenance of chemotactic stimuli. RANTES is a potent chemoattractant for leukocytes including monocytes and CD45RO+ memory T lymphocytes. The aim of this study was to determine the production, the source, and the function of antigenic RANTES in arthritis. We detected antigenic RANTES in SFs from RA and OA patients (100 +/- 22.7 and 72 +/- 30.7 pg/ml, respectively). CM from RA ST fibroblasts stimulated with interleukin-1beta or tumor necrosis factor-alpha contained significantly more antigenic RANTES than unstimulated CM (452 +/- 181.6 and 581 +/- 200.2 pg/ml, respectively, versus 12 +/- 4.4 pg/ml, P < 0.05). PHA-stimulated RA SF mononuclear cells secreted 5- to 15-fold more antigenic RANTES than did nonstimulated mononuclear cells, while LPS induced secretion up to 4-fold. We immunolocalized antigenic RANTES to sublining macrophages (28 +/- 3.7 and 8 +/- 2.0% immunopositive cells), perivascular macrophages (56 +/- 6.9 and 19 +/- 3.4%), and synovial lining cells (37 +/- 5.8 and 60 +/- 10.4%) in RA and OA tissue, respectively. Anti-RANTES neutralized 20.2 +/- 1.3% of the RA SF chemotactic activity for normal peripheral blood monocytes (P < 0.05). These results demonstrate antigenic RANTES in RA and OA ST and SF and identify RANTES as a chemoattractant for monocytes in the RA joint.
类风湿性关节炎（RA）的特征是白细胞从血管系统募集到炎症滑膜组织（ST）和滑液（SF）中，这部分取决于趋化刺激的持续维持。调节激活正常T细胞表达和分泌的趋化因子（RANTES）是包括单核细胞和CD45RO +记忆T淋巴细胞在内的白细胞的有效趋化剂。本研究的目的是确定关节炎中抗原性RANTES的产生、来源和功能。我们在RA和OA患者的SF中检测到抗原性RANTES（分别为100±22.7和72±30.7 pg/ml）。用白细胞介素-1β或肿瘤坏死因子-α刺激的RA ST成纤维细胞的条件培养基（CM）中含有的抗原性RANTES明显多于未刺激的CM（分别为452±181.6和581±200.2 pg/ml，而未刺激的为12±4.4 pg/ml，P<0.05）。PHA刺激的RA SF单核细胞分泌的抗原性RANTES比未刺激的单核细胞多5至15倍，而LPS诱导的分泌高达4倍。我们将抗原性RANTES免疫定位到RA和OA组织中的内膜下巨噬细胞（免疫阳性细胞分别为28±3.7%和8±2.0%）、血管周围巨噬细胞（56±6.9%和19±3.4%）以及滑膜衬里细胞（37±5.8%和60±10.4%）。抗RANTES中和了RA SF对正常外周血单核细胞趋化活性的20.2±1.3%（P<0.05）。这些结果证明了RA和OA的ST及SF中存在抗原性RANTES，并确定RANTES是RA关节中单核细胞的趋化剂。
