Sozzani S, Introna M, Bernasconi S, Polentarutti N, Cinque P, Poli G, Sica A, Mantovani A
Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Leukoc Biol. 1997 Jul;62(1):30-3. doi: 10.1002/jlb.62.1.30.
Monocyte chemotactic protein-1 (MCP-1) interacts with the chemokine receptor CCR2. Two CCR2 cDNAs have been described. Sequence analysis as well as Northern blotting and RNase protection with different probes revealed that the CCR2 gene is expressed in activated natural killer (NK) cells and mononuclear phagocytes as a predominant long transcript (3.4 kb) consisting of CCR2B followed by a novel sequence (X), corresponding to an intron in the genome, and by a CCR2A specific portion. The predominant long transcript is polyadenylated and present in the cytoplasm. We found that bacterial products and cytokines affect CCR2 expression. Interleukin-2 (IL-2) augmented CCR2 mRNA in monocytes and NK cells. The augmented migratory capacity of IL-2-activated versus resting NK cells was associated with increased CCR2 transcript levels. Lipopolysaccharide (LPS) and other microbial agents caused a rapid and drastic reduction of CCR2 mRNA levels. The rate of nuclear transcription of CCR2 was not affected by LPS, whereas the mRNA half life was reduced. These results suggest that regulation of receptor expression, in addition to agonist production, is probably a crucial point in the regulation of the chemokine system. Down-regulation of chemokine receptor expression may play a role in the modulation of HIV infection in macrophages by LPS. Levels of MCP-1 were markedly elevated in the cerebrospinal fluid (CSF) but not in blood of HIV-infected patients with cytomegalovirus (CMV) encephalitis. The CSF levels of MCP-1 in CMV encephalitis were markedly higher than those found in the CSF of HIV-infected patients with or without unrelated neurological diseases. IL-8, the prototype of C-X-C chemokines and RANTES and macrophage inflammatory protein-1 alpha (C-C chemokines) were not substantially increased in the liquor of CMV encephalitis patients. High levels of MCP-1 may underlie monocyte recruitment and tissue damage in CMV encephalitis and may represent a rapid and useful tool in the diagnostic armamentarium for neurological disorders associated with HIV.
单核细胞趋化蛋白-1（MCP-1）与趋化因子受体CCR2相互作用。已描述了两种CCR2 cDNA。序列分析以及用不同探针进行的Northern印迹和RNA酶保护实验表明，CCR2基因在活化的自然杀伤（NK）细胞和单核吞噬细胞中表达，主要转录本为长转录本（3.4 kb），由CCR2B、随后的一个新序列（X，对应于基因组中的一个内含子）以及CCR2A特异性部分组成。主要的长转录本进行了多聚腺苷酸化并存在于细胞质中。我们发现细菌产物和细胞因子会影响CCR2的表达。白细胞介素-2（IL-2）可增加单核细胞和NK细胞中CCR2 mRNA的水平。与静息NK细胞相比，IL-2激活的NK细胞迁移能力增强与CCR2转录水平升高有关。脂多糖（LPS）和其他微生物因子可导致CCR2 mRNA水平迅速大幅降低。CCR2的核转录速率不受LPS影响，而mRNA半衰期缩短。这些结果表明，除了激动剂产生外，受体表达的调节可能是趋化因子系统调节中的一个关键点。趋化因子受体表达的下调可能在LPS对巨噬细胞中HIV感染的调节中起作用。在患有巨细胞病毒（CMV）脑炎的HIV感染患者的脑脊液（CSF）中，MCP-1水平显著升高，但血液中未升高。CMV脑炎患者脑脊液中MCP-1的水平明显高于患有或未患有无关神经系统疾病的HIV感染患者脑脊液中的水平。C-X-C趋化因子的原型IL-8、RANTES和巨噬细胞炎性蛋白-1α（C-C趋化因子）在CMV脑炎患者的脑脊液中并未显著增加。高水平的MCP-1可能是CMV脑炎中单核细胞募集和组织损伤的基础，并且可能是与HIV相关的神经系统疾病诊断工具库中一种快速且有用的工具。
