Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis
Synovial fluid neutrophils transcribe and express class II major histocompatibility complex molecules in rheumatoid arthritis
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DOI：
10.1002/art.11253
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发表时间：
2003-10-01
影响因子：
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通讯作者：
Moots, RJ
中科院分区：
文献类型：
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作者：
Cross, A;Bucknall, RC;Moots, RJ
目标。为探讨类风湿关节炎(RA)患者外周血中中性粒细胞与T细胞之间的相互作用，确定体外诱导外周血中性粒细胞表达第二类主要组织相容性复合体(MHC)的最佳条件，并研究其表达第二类MHC分子的能力。用流式细胞仪和荧光显微镜检测正常人和类风湿关节炎患者外周血和滑液中中性粒细胞表面II类MHC及其共刺激分子的表达。用Western blotting和Northern blotting分别检测细胞内II类MHC蛋白和信使RNA(MRNA)的表达。从对照组新鲜分离的外周血中性粒细胞不表达表面II类MHC；用适当的细胞因子培养诱导表达。新鲜分离的RA患者外周血中性粒细胞表达mRNA，但不表达II型MHC。从RA患者新鲜分离的SF中性粒细胞含有高水平的II类MHC mRNA，不表达表面II类MHC，但Western blotting检测到细胞内有大量这种蛋白。体外培养20小时后，RA患者的SF中性粒细胞表达大量的表面II类MHC，但共刺激分子CD80和CD86水平很低。荧光显微镜可将表面II类MHC定位于中性粒细胞上的离散区域。结论：表达II类MHC的中性粒细胞刺激T细胞增殖。RA患者外周血中性粒细胞表达II类MHC基因。类风湿关节炎患者的SF中性粒细胞合成和表达大量的II类MHC，但不表达共刺激分子。这可能是与T细胞的一种新的相互作用的基础，这在疾病病理学方面是重要的。
Objective. To investigate a potential interaction between neutrophils and T cells in rheumatoid arthritis (RA), by defining the optimal conditions for induction of class II major histocompatibility complex (MHC) expression on peripheral blood neutrophils in vitro and investigating the capacity for neutrophils to express class II MHC molecules in RA.Methods. Surface expression of class II MHC and costimulatory molecules by peripheral blood and synovial fluid (SF) neutrophils obtained from healthy controls and patients with RA was measured by How cytometry and fluorescence microscopy. Intracellular class II MHC protein and, messenger RNA (mRNA) were detected by Western blotting and Northern blotting, respectively.Results. Freshly isolated peripheral blood neutrophils from controls did not express surface class II MHC; expression was induced by culture with appropriate cytokines. Freshly isolated peripheral blood neutrophils from patients with RA expressed mRNA, but there was no surface expression of class II MHC. Freshly isolated SF neutrophils from patients with RA contained high levels of class II MHC mRNA, did not express surface class II MHC, but did have large intracellular amounts of this protein as detected by Western blotting. After culture for 20 hours in vitro, SF neutrophils from RA patients expressed large amounts of surface class II MHC hut very low levels of costimulatory molecules CD80 and CD86. Fluorescence microscopy localized surface class II MHC to discrete areas on the neutrophil. Class II MHC-expressing neutrophils stimulated T cell proliferation.Conclusion. Peripheral blood neutrophils from patients with RA but not healthy controls express class II MHC mRNA. SF neutrophils in RA synthesize and express large amounts of class II MHC but not costimulatory molecules. This might underlie a novel interaction with T cells that is important in terms of disease pathology.