Moepps Barbara, Nuesseler Elke, Braun Mike, Gierschik Peter
Department of Pharmacology and Toxicology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Mol Immunol. 2006 Mar;43(7):897-914. doi: 10.1016/j.molimm.2005.06.043. Epub 2005 Aug 9.
Two distinct genes are present in the human genome encoding receptors for human interleukin-8 (hCXCL8), referred to as hCXCR1 and hCXCR2. While it seems clear that orthologous genes are present in the genomes of several mammals, the existence of a gene encoding an ortholog of hCXCR1 in the mouse has thus far been controversial. We have isolated a cDNA that is highly similar to the cDNAs of hCXCR1 and hCXCR2, but is clearly distinct from the cDNA encoding mouse CXCR2 (mCXCR2). The encoded protein, designated mouse CXCR1-like (mCXCR1-like), shares 64, 57, 57, and 89% identical amino acids with hCXCR1, hCXCR2, mCXCR2, and rCXCR1-like, respectively. The gene encoding mCXCR1-like was mapped to mouse chromosome 1 and its genomic organization was determined to be very similar to the organization of the gene encoding hCXCR1. Like hCXCR1, mCXCR1-like was found to be expressed at the mRNA level in neutrophils. In addition, mRNA encoding mCXCR1-like was detected in liver, kidney, and spleen. In spleen, mCXCR1-like transcripts were predominantly found in CD4+ T cells. In liver, mCXCR1-like transcripts were identified in residual CD3+ T cells and macrophages, suggesting that mCXCR1-like may regulate inflammatory and immunological processes in the liver. When expressed as a recombinant protein, mCXCR1-like was not activated by a large panel of known CXC chemokines of human and murine origin. These findings suggest that a homolog or ortholog of hCXCR1 is expressed in the mouse to be activated by a hitherto unknown CXC chemokine of the mouse.
人类基因组中存在两个不同的基因，它们编码人白细胞介素-8（hCXCL8）的受体，分别称为hCXCR1和hCXCR2。虽然很明显几种哺乳动物的基因组中存在直系同源基因，但迄今为止，小鼠中编码hCXCR1直系同源物的基因的存在一直存在争议。我们分离出了一种与hCXCR1和hCXCR2的cDNA高度相似，但与编码小鼠CXCR2（mCXCR2）的cDNA明显不同的cDNA。所编码的蛋白质命名为小鼠CXCR1样蛋白（mCXCR1样蛋白），与hCXCR1、hCXCR2、mCXCR2和rCXCR1样蛋白分别有64%、57%、57%和89%的相同氨基酸。编码mCXCR1样蛋白的基因被定位到小鼠1号染色体上，其基因组结构被确定与编码hCXCR1的基因结构非常相似。与hCXCR1一样，发现mCXCR1样蛋白在中性粒细胞的mRNA水平表达。此外，在肝脏、肾脏和脾脏中检测到了编码mCXCR1样蛋白的mRNA。在脾脏中，mCXCR1样转录本主要存在于CD4+T细胞中。在肝脏中，在残余的CD3+T细胞和巨噬细胞中鉴定出了mCXCR1样转录本，这表明mCXCR1样蛋白可能调节肝脏中的炎症和免疫过程。当作为重组蛋白表达时，mCXCR1样蛋白不会被大量已知的人和鼠源CXC趋化因子激活。这些发现表明，hCXCR1的同源物或直系同源物在小鼠中表达，可被一种迄今未知的小鼠CXC趋化因子激活。
