Blom A B, van Lent P L, van Vuuren H, Holthuysen A E, Jacobs C, van de Putte L B, van de Winkel J G, van den Berg W B
Department of Rheumatology, University Hospital St Radboud, Nijmegen.
Arthritis Res. 2000;2(6):489-503. doi: 10.1186/ar131. Epub 2000 Aug 31.
We investigated the role of Fc gamma receptors (Fc gamma Rs) on synovial macrophages in immune-complex-mediated arthritis (ICA). ICA elicited in knee joints of C57BL/6 mice caused a short-lasting, florid inflammation and reversible loss of proteoglycans (PGs), moderate chondrocyte death, and minor erosion of the cartilage. In contrast, when ICA was induced in knee joints of Fc receptor (FcR) gamma-chain(-/-) C57BL/6 mice, which lack functional Fc gamma RI and RIII, inflammation and cartilage destruction were prevented. When ICA was elicited in DBA/1 mice, a very severe, chronic inflammation was observed, and significantly more chondrocyte death and cartilage erosion than in arthritic C57BL/6 mice. The synovial lining and peritoneal macrophages of naïve DBA/1 mice expressed a significantly higher level of Fc gamma Rs than was seen in C57BL/6 mice. Moreover, elevated and prolonged expression of IL-1 was found after stimulation of these cells with immune complexes. Zymosan or streptococcal cell walls caused comparable inflammation and only mild cartilage destruction in all strains. We conclude that Fc gamma R expression on synovial macrophages may be related to the severity of synovial inflammation and cartilage destruction during ICA.
我们研究了Fcγ受体（FcγRs）在免疫复合物介导的关节炎（ICA）中滑膜巨噬细胞上的作用。在C57BL/6小鼠膝关节诱发的ICA导致短暂的、剧烈的炎症以及蛋白聚糖（PGs）的可逆性丢失、中度软骨细胞死亡和轻微的软骨侵蚀。相比之下，当在缺乏功能性FcγRI和RIII的Fc受体（FcR）γ链基因敲除（-/-）C57BL/6小鼠膝关节中诱发ICA时，炎症和软骨破坏得到了预防。当在DBA/1小鼠中诱发ICA时，观察到非常严重的慢性炎症，并且软骨细胞死亡和软骨侵蚀明显多于患关节炎的C57BL/6小鼠。未接触过抗原的DBA/1小鼠的滑膜衬里和腹膜巨噬细胞表达的FcγRs水平明显高于C57BL/6小鼠。此外，用免疫复合物刺激这些细胞后发现白细胞介素-1的表达升高且持续时间延长。酵母聚糖或链球菌细胞壁在所有品系中引起类似的炎症且仅导致轻微的软骨破坏。我们得出结论，滑膜巨噬细胞上的FcγR表达可能与ICA期间滑膜炎症和软骨破坏的严重程度有关。
