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

免疫复合物的沉积引起组织损伤的急性炎症反应。免疫复合物诱导的组织损伤是由炎症细胞浸润介导的，炎症细胞浸润受多种趋化因子的高度调节。为了评估趋化因子受体CCR1和CCR5以及这些受体的配体CCL3/巨噬细胞炎症蛋白-1α在这一致病过程中的作用，在缺乏CCR1、CCR5或CCL3的小鼠中诱导了反向被动皮肤和腹膜Arthus反应。在皮肤Arthus反应中，与野生型小鼠相比，CCR1缺陷（CCR1^<-/->）和CCL3^<-/->小鼠的水肿明显减轻，而CCR5^<-/->小鼠则没有。与野生型小鼠相比，ccr3 ^<-/->小鼠和CCR1^<-/->小鼠的浸润中性粒细胞和肥大细胞数量分别减少。CCR1和CCR5在中性粒细胞和肥大细胞上表达。值得注意的是，与野生型小鼠相比，CCR5^<-/->和CCL3^<-/->小鼠皮内CCL5/RANTES (CCR1和CCR5^<-/->小鼠皮内CCL3 mRNA表达增加，CCR1^<-/->和CCR5^<-/->小鼠皮肤CCL3 mRNA表达增加。这些结果表明，CCR1、CCR5和CCL3共同参与了皮肤Arthus反应，也表明CCL3和CCL5的表达增强弥补了CCR1、CCR5和CCL3在反应中的缺失。

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.