Role of C-C Chemokine Receptors 1 and 5 and CCL3/Macrophage Inflammatory Protein-la in the Cutaneous Arthus Reaction

免疫复合体的沉积可引起急性炎症反应，造成组织损伤。免疫复合体诱导的组织损伤是由多种趋化因子高度调控的炎性细胞浸润所介导的。为了评估趋化因子受体CCR1和CCR5以及这些受体的配体CCL3/巨噬细胞炎性蛋白-1α在这一致病过程中的作用，我们在缺乏CCR1CCR5或CCL3的小鼠身上诱导了反向被动的皮肤和腹膜阿尔萨斯反应。在皮肤阿尔萨斯反应中，与野生型小鼠相比，CCR1缺陷小鼠(CCR1^&lt；-/-&gt；)和CCL3^&lt；-/-&gt；小鼠的水肿显著减轻，但CCR5^&lt；-/-&gt；小鼠的肿胀没有明显减轻。与野生型小鼠相比，CCL3^&lt；-/-&gt；和CCR1^&lt；-/-&gt；小鼠的中性粒细胞和肥大细胞数量分别减少。中性粒细胞和肥大细胞表达CCR1和CCR5。与野生型小鼠相比，CCR5和CCR5的另一个配体CCL5/RANTES在皮内的mRNA表达显著增加，而CCR5和CCR5的皮肤CCL3mRNA的表达显著增加。这些结果表明，CCR1、CCR5和CCL3共同参与了皮肤Arthes反应，并提示CCL3和CCL5的表达增强补偿了CCR1、CCR5和CCL3在反应中的丢失。

The deposition of immune complexes induces an acute inflammatory response with tissue injury. Immune complex-induced tissue injury is mediated by inflammatory cell infiltration that is highly regulated by multiple chemokines. To assess the role of chemokine receptors, CCR1 and CCR5, and a ligand for these receptors, CCL3/macrophage inflammatory protein-1α, in this pathogenic process, the reverse passive cutaneous and peritoneal Arthus reaction was induced in mice lacking CCR1, CCR5, or CCL3. In the cutaneous Arthus reaction, edema was significantly attenuated in CCR1-deficient (CCR1^<-/->) and CCL3^<-/-> mice but not CCR5^<-/-> mice, compared with wild-type mice. Numbers of infiltrating neutrophils and mast cells were reduced in CCL3^<-/-> and CCR1^<-/-> mice, respectively, compared with wild-type mice. CCR1 and CCR5 were expressed on neutrophils and mast cells. Remarkably, the intradermal mRNA expression of CCL5/RANTES, another ligand for CCR1 and 5, was increased in CCR5^<-/-> and CCL3^<-/-> mice, compared with wild-type mice, while the cutaneous CCL3 mRNA expression was augmented in CCR1^<-/-> and CCR5^<-/-> mice. These results indicate that CCR1, CCR5, and CCL3 cooperatively contribute to the cutaneous Arthus reaction and also suggest that enhanced expression of CCL3 and CCL5 compensates for the loss of CCR1, CCR5, and CCL3 in the reaction.