C—C亚族趋化因子与糖尿病肾病

C-C亚族趋化因子主要趋化和激活单核细胞及某些T细胞亚群，对嗜酸性粒细胞、嗜碱性粒细胞以及自然杀伤细胞亦有不同作用，进而参与炎症过程。其中单核细胞趋化蛋白(MCP)—1和正常T细胞活化后表达和分泌的调节蛋白(RANTES)是巨噬细胞的特异性趋化因子，高糖、糖化血红蛋白及肾素—血管紧张素系统可促进其高表达，从而使巨噬细胞在肾脏聚集和活化，在糖尿病肾病肾小球硬化以及肾小管间质纤维化的发生、发展中发挥着重要作用。其中，核因子—κB可能参与了高糖对MCP—1的上调作用。     

CXCR3 CCR5及其配体在类风湿关节炎患者滑液和外周血中的表达

目的 在单细胞水平上，研究类风湿关节炎（RA）患者滑液及外周血中单核/巨噬细胞，T淋巴细胞上趋化因子受体CCR5及ＣＸＣＲ３的表达。并测定CCR5的配体MIP-1β。激活正常T细胞表达和分泌因子（RANTES）及T细胞亚群，探讨其在RA发病中的作用机制。方法 分离RA患者滑液单个核细胞（SFMC），外周血单个核细胞（PBMC）及正常人PBMC（对照），以三色荧光素标记物进行流式细胞术分析CD14^ ,CD3^ 细胞膜表面趋化因子受体CCR5，CCR3及细胞内趋化因子MIP-1β，RANTES和细胞因子白细胞介素（IL）-4，干扰素（IFN）-γ的表达率。结果 与PBMC相比，RA患者SFMC中的单核/巨噬细胞，T细胞上趋化因子受体CCR4及CEXR3表达显著增高；且单核/巨噬细胞分泌趋化因子MIP-1β，RANTES的百分比较高；SFMC中Th1细胞亚群（即IFN-γ^ T细胞）的表达率与滑液及外周血中T淋巴细胞上趋化因子受体CCR4及CXCR3的表达率显著相关。结论 趋化因子受体CCR5^ ,CXCR3^ 的单核/巨噬细胞，T细胞积聚在RA患者的病变关节内，且单核/巨噬细胞分泌较多趋化因子；CCR5，CXCR3可能参与调节细胞移动。与Th1细胞亚群及其“伙伴”细胞在RA关节内积聚有关；可能与RA的发病相关。     

单核／巨噬细胞及其趋化因子与脑缺血再灌注损伤

缺血再灌注能诱导脑组织表达单核细胞趋化因子－１（ＭＣＰ－１）和巨噬细胞炎性蛋白－１（ＭＩＰ－１），并伴有单核／巨噬细胞的浸润和活活。一方面，这些趋化因子的表达和单核／巨噬细胞的激活有助于增强机体抵抗力，参与组织修复，是机体防御反应的重要组成部分；另一方面，又可加重组织损伤。文章论述了单核／巨噬细胞及其趋化因子ＭＰＣ－１和ＭＩＰ－１在脑缺血再灌注损伤中的作用。     

MCP-1及其基因多态性与糖尿病肾病的关系

糖尿病肾病（DN）的发病机制比较复杂,至今尚未完全阐明,可能与遗传易感性、糖代谢紊乱、细胞因子、炎症机制等多种因素有关[1]。近年研究发现,DN可能和单核巨噬细胞在肾组织的广泛浸润有关。而单核细胞趋化蛋白-1（MCP-1）是单核巨噬细胞特异性趋化因子,是单核巨噬细胞聚集活化的主要因素[2]。本文结合文献就MCP-1及其基因多态性（SNP）与DN的关系作一综述。     

狼疮易感基因IFIT1调控巨噬细胞趋化因子表达初探

目的 研究IFIT1对小鼠巨噬细胞系趋化因子产生的影响,探讨其在系统性红斑狼疮(SLE)中的致病机制.方法 电转染法在RAW264.7细胞系中瞬时转染IFIT1,实时荧光定量聚合酶链反应(realtime-PCR)检测IFIT1过表达对该细胞趋化因子巨噬细胞炎症蛋白(MIP)-1α、RANTES、CCL9、CX-CL2和IP-10表达的影响;同时检测NZB/NZW F1小鼠肾组织上述趋化因子表达水平.结果 瞬时转染musIFIT1的RAW264.7小鼠巨噬细胞上述趋化因子表达水平均较对照细胞明显增高,LPS刺激后4 h及24 h表达进一步增高.与正常对照BALB/c小鼠相比,NZB/NZW F1小鼠肾组织中上述趋化因子表达增高.结论 狼疮易感摹因IFIT1可促进巨噬细胞趋化因子MIP-1α、RANTES、CCL9、CXCL2和IP-10的表达,从而可能参与了SLE局部脏器的免疫损伤.     

单核/巨噬细胞及其趋化因子与脑缺血再灌注损伤

缺血再灌注能诱导脑组织表达单核细胞趋化因子 1(MCP 1)和巨噬细胞炎性蛋白 1(MIP 1) ,并伴有单核 /巨噬细胞的浸润和激活。一方面 ,这些趋化因子的表达和单核 /巨噬细胞的激活有助于增强机体抵抗力 ,参与组织修复 ,是机体防御反应的重要组成部分 ;另一方面 ,又可加重组织损伤。文章论述了单核 /巨噬细胞及其趋化因子MCP 1和MIP 1在脑缺血再灌注损伤中的作用     

C-C亚族趋化因子与糖尿病肾病

C-C亚族趋化因子主要趋化和激活单核细胞及某些T细胞亚群,对嗜酸性粒细胞、嗜碱性粒细胞以及自然杀伤细胞亦有不同作用,进而参与炎症过程。其中单核细胞趋化蛋白(MCP)-1和正常T细胞活化后表达和分泌的调节蛋白(RANTES)是巨噬细胞的特异性趋化因子,高糖、糖化血红蛋白及肾素-血管紧张素系统可促进其高表达,从而使巨噬细胞在肾脏聚集和活化,在糖尿病肾病肾小球硬化以及肾小管间质纤维化的发生、发展中发挥着重要作用。其中,核因子-κB可能参与了高糖对MCP-1的上调作用。     

趋化因子促进冠状动脉粥样硬化斑块不稳定的分子机制

目的 研究单核细胞趋化因子在动脉粥样硬化斑块不稳定中作用的分子机制。方法 对50例稳定性心绞痛(SAP)和50例不稳定性心绞痛(UAP)患者分别进行冠状动脉造影(CAG)和血管内超声(IVUS)检查。应用Transwell小室检测2组患者血单核细胞的趋化活性,ELISA法检测血清中高敏C反应蛋白(hs-CRP)、单核细胞趋化蛋白-1(MCP-1)、T细胞表达和分泌因子(RANTES)和Fractalkine的水平,用实时PCR检测单核细胞中MCP-1、RANTES和Fractalkine的mRNA表达水平。结果 IVUS共检出SAP组85处斑块,UAP组90处斑块,其中,UAP组主要为脂质性斑块48％ (43/90),而SAP组主要为纤维性斑块54％ (46/85),脂质斑块仅占16％( 14/85)。与SAP组比较,UAP组斑块负荷和血管重构指数明显大于前者（P均＜0.01）。UAP组单核细胞趋化活性明显增强,单核细胞移动数量明显多于SAP组,两组比较差异有统计学意义(P＜0.01)。UAP组血清中hs-CRP、MCP-1、RANTES和Fractalkine水平明显高于SAP组（P＜0.05或P＜0.01）。UAP组MCP-1、RANTES和Fractalkine的mRNA表达水平明显高于SAP组(P＜0.05)。结论 单核细胞趋化因子MCP-1、RANTES和Fractalkine可能促进了冠状动脉粥样硬化斑块的不稳定。     

白细胞介素10对巨噬细胞源泡沫细胞趋化因子表达的影响

目的探讨白细胞介素10对单核-巨噬细胞源性泡沫细胞转化过程中趋化因子表达的影响及其机制。方法以佛波醇酯诱导THP-1单核细胞分化为巨噬细胞，在氧化型低密度脂蛋白作用下形成泡沫细胞，同时给予白细胞介素10干预，采用逆转录聚合酶链反应和凝胶阻滞试验研究单核细胞趋化蛋白1、巨噬细胞炎性蛋白5、白细胞介素8mRNA的表达变化及白细胞介素10对核因子KB活性的影响。结果在白细胞介素10作用下，泡沫细胞中单核细胞趋化蛋白1和巨噬细胞炎性蛋白5mRNA相对表达量均显著降低，且与作用时间成正相关，而白细胞介素8相对表达量变化不明显。同时白细胞介素10能显著抑制氧化型低密度脂蛋白诱导的核因子KB活化。结论白细胞介素10选择性抑制单核-巨噬细胞源性泡沫细胞形成中趋化因子mRNA的表达与有效地抑制核因子KB活性密切相关。这对降低炎症反应。减少泡沫细胞形成，延缓动脉粥样斑块形成具有重要意义。     

单核细胞趋化蛋白—1和糖尿病肾病

糖尿病肾病（DN）往往存在着血糖、血脂的代谢紊乱及某些细胞因子（白介素－1、肿瘤坏死因子－α）和血管紧张素Ⅱ水平的升高，这些改变均可使体内单核细胞趋化因子－1（MCP－1）水平上升。MCP-1一种对单核细胞有强烈趋化作用的细胞因子，它的增多使肾小球中单核浸润，导致细胞外基质在肾小球和肾小管中堆积。因此MCP-1在DN的发生、发展中起重要作用。     

Aging is associated with increased T-cell chemokine expression in C57BL/6 mice

To better understand the contribution of the chemokine system in immune senescence, we determined the aging effect on CD4+ and CD8+ T-cell chemokine expression by microarray screening and ribonuclease protection assays. Compared with young C57BL/6 mice, freshly isolated CD4+ cells from aged mice express increased level of interferon-gamma-inducible protein 10 (IP-10), macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated upon activation, normal T-cell expressed and secreted (RANTES), and lymphotactin (Ltn). T-cell receptor (TCR)/coreceptor stimulation up-regulates MIP-1alpha, MIP-1beta, and Ltn, and down-regulates IP-10 and RANTES expression in CD4+ T cells. A similar increase in chemokine expression was demonstrated in the CD8+ T cell. Enzyme-linked immunosorbent assays confirmed increased T-cell chemokine protein production in old CD4+ and CD8+ T cells. Finally, supernatant of cultured T cells from old animals caused an enhanced leukocyte chemotaxis response compared with that from young animals, suggesting that the age-related difference in T-cell chemokine expression has an important functional consequence.     

Fas signal links innate and adaptive immunity by promoting dendritic-cell secretion of CC and CXC chemokines

Dendritic cells (DCs) and chemokines are important in linking innate and adaptive immunity. We previously reported that Fas ligation induced interleukin 1beta (IL-1beta)-dependent maturation and IL-1beta-independent survival of DCs, with extracellular signal-regulated kinase (ERK) and nuclear factor-kappaB (NF-kappaB) signaling pathways involved, respectively. We describe here that Fas ligation induced DCs to rapidly produce both CXC and CC chemokines, including macrophage inflammatory protein 2 (MIP-2), MIP-1alpha, MIP-1beta, monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation normal T cell expressed and secreted), and TARC (thymus and activation-regulated chemokine), resulting in enhanced chemoattraction of neutrophils and T cells by Fas-ligated DCs in vivo or by its supernatant in vitro. These chemokines work synergistically in chemoattraction of neutrophils and T cells with MIP-2 more important for neutrophils, MIP-1alpha and TARC more important for T cells. Moreover, Fas-ligated DCs increased endocytosis by neutrophils and activation and proliferation of antigen-specific naive T cells. Fas ligation-induced DC secretion of chemokines involves Ras/Raf/mitogen-activated protein kinase kinase (MEK)/ERK activation and is ERK, but not NF-kappaB, dependent. Activation of caspases, including caspase 1, but not IL-1 autocrine action, is involved in this process. These data indicate that Fas signaling provides a key link between innate response and adaptive immunity by promoting DC chemokine production.     

CC chemokines and the receptors CCR3 and CCR5 are differentially expressed in the nonneoplastic leukocytic infiltrates of Hodgkin disease

Lymph nodes with Hodgkin disease (HD) harbor few neoplastic cells in a marked leukocytic infiltrate. Since chemokines are likely to be involved in the recruitment of these leukocytes, the expression of potentially relevant chemokines and chemokine receptors were studied in lymph nodes from 24 patients with HD and in 5 control lymph nodes. The expression of regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta was analyzed by in situ hybridization and that of CCR3 and CCR5 by immunohistochemistry and flow cytometry. It was found that, overall, the expression of all 4 chemokines was markedly enhanced, but the cellular source was different. RANTES was expressed almost exclusively by T cells whereas the expression of MCP-1, MIP-1alpha, and MIP-1beta was confined largely to macrophages. In control lymph nodes, chemokine expression was low, with the exception of MIP-1alpha in macrophages. CCR3 and CCR5 were highly expressed in T cells of HD involved but not of control lymph nodes. CCR3 was equally distributed in CD4+ and CD8+ cells, but CCR5 was associated largely with CD4+ cells. In HD lymph nodes, CCR3 and CCR5 were also expressed in B cells, which normally do not express these receptors. All these chemokines and receptors studied, by contrast, were absent in the neoplastic cells. It was concluded that chemokines are involved in the formation of the HD nonneoplastic leukocytic infiltrate. Expression of CCR3 and CCR5 appears to be characteristic of HD, but the roles of these receptors' up-regulation for the disease process remain unclear.     

Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5

CC chemokine receptor 5 (CCR5) is a coreceptor for cellular entry of monocyte-tropic (R5) strains of human immunodeficiency virus (HIV) type 1, which has been implicated as the predominant phenotype of HIV in early infection. The CCR5 agonists macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and RANTES (regulated on activation, normally T cell-expressed and -secreted) have been shown to block replication of R5 virus in vitro and have gained attention as potential antiviral factors. However, a few reports have suggested that other chemokines may also block R5 HIV-1, including monocyte chemoattractant protein (MCP)-2 (CC chemokine ligand 8). We demonstrate that MCP-2 specifically inhibits replication of R5 HIV-1 and that this activity is additive to that of RANTES. Furthermore, MCP-2 induces a robust, pertussis toxin-sensitive calcium flux in primary lymphocytes, and cross-desensitization studies indicate that MCP-2 acts via CCR5. These data confirm that MCP-2 is a ligand for CCR5 on CD4(+) lymphocytes and can specifically block R5 HIV-1.     

Chemokine receptor expression in rat adjuvant-induced arthritis

OBJECTIVE: Chemokine receptors mediate leukocyte migration into inflamed rheumatoid arthritis (RA) synovial tissue (ST). Knowledge of their distribution is crucial for understanding the evolution of the inflammatory process. In this study, we used rat adjuvant-induced arthritis (AIA), a model for RA, to define the temporospatial expression of chemokine receptors. METHODS: ST from rats with AIA was immunostained, the percentage of cells expressing each receptor was determined, and findings were correlated with levels of inflammation. Chemokine receptor expression was evaluated on rat macrophages in vitro. RESULTS: CCR1, a receptor for macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 and RANTES/CCL5, exhibited high constitutive expression on macrophages in AIA. CCR5, binding MIP-1alpha/CCL3 and RANTES/CCL5, was up-regulated on ST macrophages during the course of AIA, correlating with macrophage expression of CCR2, a receptor for monocyte chemoattractant protein 1/CCL2. Endothelial cell (EC) CCR2 was down-regulated as arthritis progressed, inversely correlating with inflammation. CCR3, another RANTES/CCL5 receptor, was constitutively high on macrophages in vivo and in vitro, with down-regulation during AIA. CXCR4, a receptor for stromal cell-derived factor 1/CXCL12), was prominently up-regulated on ECs, preceding the peak of inflammation. CONCLUSION: These findings show that 1) constitutive expression of CCR1 on macrophages remains high during AIA; 2) CCR2 and CCR3 may play a role in initial recruitment of leukocytes to ST in AIA; 3) macrophage expression of CCR2 and CCR5 may be important for sustaining inflammatory changes; and 4) EC CXCR4 may be a harbinger of inflammatory changes. Our results may help guide chemokine receptor blockade-targeting treatment strategies in inflammatory arthritis.