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

免疫复合物的沉积诱导急性炎症反应和组织损伤。免疫复合物诱导的组织损伤由炎性细胞浸润介导，炎性细胞浸润受多种趋化因子高度调节。为了评估趋化因子受体CCR 1和CCR 5以及这些受体的配体CCL 3/巨噬细胞炎性蛋白-1 α在该致病过程中的作用，在缺乏CCR 1、CCR 5或CCL 3的小鼠中诱导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，CCR 1缺陷型（CCR 1 ^-/->）和CCL 3 ^-/->小鼠的水肿显著减轻，但CCR 5 ^-/->小鼠的水肿没有减轻。与野生型小鼠相比，CCL 3 ^<-/->和CCR 1 ^<-/->小鼠中浸润的中性粒细胞和肥大细胞的数量分别减少。CCR 1和CCR 5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，CCR 5 ^<-/->和CCL 3 ^<-/->小鼠中CCL 5/RANTES（CCR 1和5的另一种配体）的皮内mRNA表达增加，而CCR 1 ^<-/->和CCR 5 ^<-/->小鼠中皮肤CCL 3 mRNA表达增加。这些结果表明，CCR 1，CCR 5，和CCL 3协同有助于皮肤Arthus反应，也表明，CCL 3和CCL 5的表达增强补偿的损失CCR 1，CCR 5，和CCL 3的反应。

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.