Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis.
Cytokines in chronic inflammatory arthritis. IV. Granulocyte/macrophage colony-stimulating factor-mediated induction of class II MHC antigen on human monocytes: a possible role in rheumatoid arthritis.
复制标题
慢性炎性关节炎中的细胞因子。 iv。粒细胞/巨噬细胞刺激因子介导的II类MHC抗原对人单核细胞的诱导：类风湿关节炎中的可能作用。
DOI：
10.1084/jem.170.3.865
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发表时间：
1989-09-01
影响因子：
15.3
通讯作者：
Firestein, G S
中科院分区：
文献类型：
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作者：
Alvaro-Gracia, J M;Zvaifler, N J;Firestein, G S
粒细胞/巨噬细胞CSF（GM-CSF）最近已被确定在类风湿关节炎（RA）滑膜积液。为了研究GM-CSF和其他细胞因子对诱导单核细胞和滑膜巨噬细胞HLA-DR表达的潜在作用，我们通过FACS分析分析了重组人细胞因子诱导正常外周血单核细胞表面II类MHC抗原表达的相对能力。GM-CSF（800 U/ml）（平均荧光通道为对照的2.54 +/-0.33倍，p小于0.001）和IFN-γ（100 U/ml）（5.14 +/- 0.60，p小于0.001）是HLA-DR最有效的诱导剂。TNF-α和IL-4也增加HLA-DR表达，尽管程度较低[分别为1.31 +/- 0.06（p小于0.02）和1.20 +/- 0.03（p小于0.01）]。IL-1（40 U/ml）、IL-2（10 ng/ml）、IL-3（50 U/ml）、IL-6（100 U/ml）和CSF-1（1，000 U/ml）不影响表面HLA-DR密度。GM-CSF还增加HLA-DR mRNA表达和表面HLA-DQ表达，但降低CD 14（单核细胞/巨噬细胞抗原）表达。GM-CSF对HLA-DR的作用不是通过体外产生IFN-γ介导的，因为它不被抗IFN-γ mAb阻断。GM-CSF与IL-4和低量（小于3U/ml）IFN-γ相加，并与TNF-α协同。因为我们最近报道了培养的RA滑膜细胞的上清液产生诱导单核细胞上HLA-DR的非IFN-γ因子，所以我们尝试用特异性抗GM-CSF mAb中和该因子。研究了四种单独的滑膜组织上清液，并且抗体中和了每种中的HLA-DR诱导因子（p小于0.01）。
Granulocyte/macrophage CSF (GM-CSF) has recently been identified in rheumatoid arthritis (RA) synovial effusions. To study a potential role for GM-CSF and other cytokines on the induction of HLA-DR expression on monocytes and synovial macrophages, we analyzed the relative ability of recombinant human cytokines to induce the surface expression of class II MHC antigens on normal peripheral blood monocytes by FACS analysis. GM-CSF (800 U/ml) (mean fluorescence channel 2.54 +/- 0.33 times the control, p less than 0.001) and IFN-gamma (100 U/ml) (5.14 +/- 0.60, p less than 0.001) were the most potent inducers of HLA-DR. TNF-alpha and IL-4 also increased HLA-DR expression, although to a lesser degree [1.31 +/- 0.06 (p less than 0.02) and 1.20 +/- 0.03 (p less than 0.01), respectively]. IL-1 (40 U/ml), IL-2 (10 ng/ml), IL-3 (50 U/ml), IL-6 (100 U/ml), and CSF-1 (1,000 U/ml) did not affect surface HLA-DR density. GM-CSF also increased HLA-DR mRNA expression and surface HLA- DQ expression, but decreased CD14 (a monocyte/macrophage antigen) expression. The effect of GM-CSF on HLA-DR was not mediated by the generation of IFN-gamma in vitro because it was not blocked by anti-IFN- gamma mAb. GM-CSF was additive with IL-4 and low amounts (less than 3 U/ml) of IFN-gamma and synergistic with TNF-alpha. Because we have recently reported that supernatants of cultured RA synovial cells produce a non-IFN-gamma factor that induces HLA-DR on monocytes, we then attempted to neutralize this factor with specific anti-GM-CSF mAb. Four separate synovial tissue supernatants were studied, and the antibody neutralized the HLA-DR-inducing factor in each (p less than 0.01).