Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis
Inflammation is preceded by tumor necrosis factor-dependent infiltration of mesenchymal cells in experimental arthritis
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DOI：
10.1002/art.10126
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发表时间：
2002-02-01
影响因子：
--
通讯作者：
Zvaifler, NJ
中科院分区：
文献类型：
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作者：
Marinova-Mutafchieva, L;Williams, RO;Zvaifler, NJ
目标。目的：探讨间充质祖细胞在胶原诱导关节炎（CIA）中的作用。采用佐剂或单独佐剂对DBA/1小鼠进行11型胶原免疫，采用免疫组织化学方法研究了关节炎前期小鼠关节内间充质细胞的存在。刺激后第10天（关节炎发病前至少10天）的关节分析显示滑膜增生，无白细胞浸润。表达骨形态发生蛋白受体（BMPRs）的大而圆的细胞，作为原始间充质细胞的标记，在关节附近的骨髓、滑膜本身以及连接骨髓和滑膜的扩大的骨管中数量增加。在给予不含胶原的佐剂的小鼠中观察到类似的变化。抗肿瘤坏死因子（anti-TNF）治疗消除了佐剂诱导的BMPR+细胞浸润和骨管增大，并且在TNFR p55/p75（-/-）小鼠中不存在。在未免疫TNF转基因小鼠中观察到骨髓细胞数量增加和骨管增大（自发发生关节炎）。这些发现表明，在CIA中，存在一个抗原不依赖的（先天的）关节炎前阶段，为随后的免疫介导的关节炎做好关节准备。诱导期涉及骨髓来源的间充质细胞，需要TNF的存在。
Objective. To determine the involvement of mesenchymal progenitor cells in the induction of collagen-induced arthritis (CIA).Methods. DBA/1 mice were immunized with type 11 collagen in adjuvant or adjuvant alone, and the presence of mesenchymal cells in the joints of prearthritic mice was studied by immunohistochemistry.Results. An analysis of the joints on day 10 postimmunization (at least 10 days before the onset of arthritis) revealed synovial hyperplasia without leukocytic infiltration. Large, round cells expressing bone morphogenetic protein receptors (BMPRs), which serve as markers for primitive mesenchymal cells, were present in increased numbers in the bone marrow adjacent to the joint, in the synovium itself, and within enlarged bone canals that connect the bone marrow to the synovium. Similar changes were observed in mice given adjuvant without collagen. Adjuvant-induced infiltration of BMPR+ cells and enlargement of bone canals were abrogated by anti-tumor necrosis factor (anti-TNF) treatment and were absent in TNFR p55/p75(-/-) mice. Increased numbers of bone marrow cells and enlarged bone canals were observed in nonimmunized TNF transgenic mice (which spontaneously develop arthritis).Conclusion. These findings suggest that in CIA, there is an antigen-independent (innate) prearthritic phase that prepares the joint for the subsequent immune-mediated arthritis. The induction phase involves marrow-derived mesenchymal cells and requires the presence of TNF.