COLLAGEN ARTHRITIS IN THE RAT IS INITIATED BY CD4+ T-CELLS AND CAN BE AMPLIFIED BY IRON
COLLAGEN ARTHRITIS IN THE RAT IS INITIATED BY CD4+ T-CELLS AND CAN BE AMPLIFIED BY IRON
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DOI：
10.1016/0008-8749(89)90001-4
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发表时间：
1989-06-01
影响因子：
4.3
通讯作者：
TRENTHAM, DE
中科院分区：
文献类型：
--
作者：
BREEDVELD, FC;DYNESIUSTRENTHAM, R;TRENTHAM, DE
通过给予年龄匹配的雌性Sprague-Dawley大鼠柠檬酸铁（Fe-cit），研究了铁在关节炎中的作用，这些大鼠在第0天接种了鸡II型胶原蛋白。大鼠在免疫后的不同天数内静脉注射铁柠檬酸钠（7.7 mg/kg体重）或相同浓度的柠檬酸钠。转铁蛋白饱和度在fe -cit后1小时达到峰值（88-95%），并在24小时内恢复到基线值。在第3天、第5天注射Fe-cit，而在第7天、第9天注射Fe-cit，均显著增加关节炎的发生率（P < 0.03）。从髌下脂肪垫中取出滑膜，于第0-10天进行免疫细胞化学分析。未静脉注射胶原免疫后大鼠滑膜的初始形态学变化是血管周围区域CD4+和转铁蛋白受体+单核细胞数量的增加；与第0天相比，这两种细胞类型在第3天都增加了2到3倍。第7天，CD8+单核细胞增多，第一批多形核白细胞出现。这些改变导致CD4-CD8比值在第3天达到峰值，此后逐渐下降。虽然Fe-cit促进了这些单核细胞的进入，但它并没有显著改变CD4-CD8的比例，也没有招募多形核白细胞进入关节组织。免疫20天后用酶联免疫吸附法测定的血清II型胶原抗体滴度，以及第23天用放射耳法测定的对胶原的延迟型超敏反应，在两组之间没有显著差异。这些发现不仅表明胶原性关节炎的初始滑膜内事件是CD4+ T细胞亚群成员在血管周围浸润，表现出活化的表型标志，还表明在免疫后的关键时间给铁增强了胶原性关节炎的诱导。这一短暂的敏感性与滑膜内最大CD4-CD8比值的巧合，以及它发生在中性粒细胞浸润阶段之前，与铁的增强作用是由诱导剂T细胞亚群介导的可能性一致。
The role of iron in arthritis was studied by administering ferric citrate (Fe-cit) to age-matched, female Sprague-Dawley rats immunized with chick type II collagen on Day 0. Rats received intravenously (iv) either Fe-cit (7.7 mg/kg body wt) or an identical concentration of sodium citrate on varying days after immunization. Transferrin saturation peaked (88-95%) 1 hr post-Fe-cit and returned to baseline values within 24 hr. Injection of Fe-cit on either Day 3 or Day 5, but not on Day 7 or Day 9, significantly (P < 0.03) increased the incidence of arthritis. Synovium from the infrapatellar fat pad was harvested on days 0-10 for analysis by immunocytochemistry. The inceptual morphologic change in the synovium following collagen immunization in rats not injected iv was an increase in the number of CD4+ and transferrin receptor+mononuclear cells in perivascular regions; compared to Day 0 both cell types had increased two- to three-fold by Day 3. On Day 7, an increase in CD8+ mononuclear cells occurred and the first polymorphonuclear leukocytes were noted. These alterations resulted in a peak in the CD4-CD8 ratio on Day 3, with a gradual decline thereafter. Although Fe-cit administration promoted the ingress of these mononuclear cells, it did not change the CD4-CD8 ratio significantly or recruit polymorphonuclear leukocytes into the joint tissue. Serum antibody titers to type II collagen, measured 20 days after immunization by an enzyme-linked immunosorbent assay, and delayed-type hypersensitivity to collagen, measured by a radiometric ear assay on Day 23, did not differ significantly between the groups. As well as showing that the initial intrasynovial event in collagen arthritis is perivascular infiltration by members of the CD4+ T cell subset displaying a phenotypic sign of activation, these findings demonstrate that iron administered at a critical time after immunization enhances the induction of collagen arthritis. The coincidence of this brief period of susceptibility with maximum CD4-CD8 ratios within the synovium and its occurrence prior to the stage of neutrophil infiltration are consistent with the possibility that the augmenting effect of iron is mediated by the inducer T cell subset.