神经源性分化蛋白在胰腺癌中的表达和意义

目的 探讨神经源性分化蛋白(NeuroD)在胰腺外分泌癌中的表达及其意义.方法 应用组织芯片和免疫组织化学EnVision二步法研究NeuroD、增殖细胞核抗原(PCNA)、p53在127例胰腺外分泌癌中的表达情况,并在光镜下观察胰腺癌神经组织浸润、神经周围淋巴细胞套、癌旁慢性胰腺炎、胰周淋巴结转移情况.分析NeuroD的表达与上述其他指标及性别、年龄、肿瘤部位、肿瘤组织学类型及分化程度等的关系.结果 NeuroD、PCNA和p53蛋白在胰腺癌组织中的阳性率分别为64.6％(82/127)、57.5％ (73/127)和59.1％ (75/127),与菲癌组织[分别为10.5％ (8/76)、9.2％(7/76)和9.2％(7/76)]相比,差异有统计学意义(P＜0.01).NeuroD蛋白的表达与PCNA、p53蛋白的表达和胰腺癌肿瘤神经浸润之间有统计学相关性(P＜0.05),而与性别、年龄、肿瘤部位、肿瘤组织学类型及分化程度、癌旁慢性胰腺炎、神经周围淋巴细胞套和淋巴结转移均等无统计学相关性(P＞0.05).结论 NeuroD蛋白在胰腺癌中呈高表达,可能参与了胰腺癌的发生和进展,并且与胰腺癌的增殖、p53信号通路和肿瘤神经浸润之间密切相关.     

ILK在胰腺癌中的表达及临床病理意义

目的研究整合素连接激酶(ILK)在胰腺癌中的表达情况及其与临床病理特征的关系。方法利用免疫组织化学方法和Western Blot方法检测61例胰腺癌标本,26例癌旁组织,4例正常胰腺组织中ILK蛋白的表达情况,并统计分析其表达率与临床病理学特征的相关性。结果免疫组织化学染色示ILK蛋白定位于细胞浆,其表达率为65.6%,其中7例Ⅲ期胰腺癌中有6例ILK染色强度均呈(+++);26例癌旁组织中有3例阳性表达,表达率11.5%;4例正常胰腺组织未见ILK的表达,胰腺癌组织的ILK表达明显高于可配对癌旁组织(P0.05)及正常胰腺组织(P0.01)。Western Blot检测发现胰腺癌组织ILK蛋白的表达水平明显高于癌旁组织(P0.01)。结论 ILK高表达与胰腺癌患者病理类型中的分化程度无关,而与肿瘤的淋巴结转移、临床分期密切相关。     

iASPP和caspase-9在食管癌组织中的表达及临床意义

目的探讨p53凋亡刺激蛋白家族抑制成员(iASPP)和caspase-9在食管癌中表达与食管癌临床病理特征的关系。方法收集临床食管癌标本85例及30例癌旁正常组织,采用免疫组织化学SP染色法和反转录PCR(RT-PCR)法检测iASPP和caspase-9在食管癌组织和癌旁正常组织中蛋白和mRNA表达情况,分析iASPP和caspase-9表达与食管癌临床病理特征之间的相关性。结果 SP法染色显示iASPP在食管癌组织和正常组织中的阳性表达率分别为72.9%(62/85)、16.7%(5/30),caspase-9在食管癌组织和正常组织中的阳性表达率分别为18.8%(16/85)、76.7%(23/30),二者差异均具有统计学意义(P0.01)。RT-PCR显示在食管癌中iASPP高表达和caspase-9低表达与食管癌的浸润深度、淋巴结转移、临床TNM分期相关(P0.05),而与食管癌患者的性别、年龄、肿瘤大小、组织类型均无相关性(P0.05),在食管癌组织中,iASPP和caspase-9的表达呈负相关(P0.05)。结论 iASPP和caspase-9在食管癌中的不同表达与食管癌的浸润深度、淋巴结转移、临床TNM分期显著相关,且二者呈负相关。     

血管内皮生长因子C和趋化因子受体CCR7的表达与膀胱癌淋巴结转移之间的关系

目的观察血管内皮生长因子(VEGF)-C和趋化因子受体CCR7在膀胱移行细胞癌组织内的表达情况,分析VEGF-C和CCR7表达与癌淋巴结转移之间的关系。方法取膀胱癌病例60例,其中,淋巴结转移组36例,无淋巴结转移组24例。应用免疫组化法和Western blot技术观察VEGF-C和CCR7在膀胱癌组织内的表达。结果 VEGF-C和CCR7主要表达于膀胱癌细胞胞浆或/和胞膜内,二者在淋巴结转移组的表达率明显高于无淋巴结转移组。VEGF-C和CCR7蛋白同时表达在淋巴结转移组和非淋巴结转移组中的表达率分别为61.1%和33.3%,VEGF-C和CCR7的表达具有显著的相关性,联合检测VEGF-C和CCR7诊断膀胱癌淋巴结转移具有较高的准确度,ROC曲线下面积达0.708。结论 VEGF-C和CCR7在促进膀胱癌淋巴结转移中可能具有一定的协同作用,二者联合检测有助于膀胱癌淋巴结转移的早期诊断     

自噬相关基因LC3、Beclin-1在胰腺癌组织中的表达及意义

目的探讨自噬相关基因LC3和Beclin-1在胰腺癌及正常胰腺组织中的表达及与胰腺癌发生、发展的相关性及意义。方法应用组织芯片技术和免疫组化法观察自噬相关蛋白LC3和Beclin-1在88例胰腺癌组织和11例正常胰腺组织中的表达,分析两者表达与临床病理特征及预后的关系。结果胰腺癌组织中LC3和Beclin-1蛋白高表达率(25%、52. 3%)显著低于正常胰腺组织(72. 7%、90. 9%),差异均有统计学意义(P=0. 003 7,P=0. 034 4)。LC3蛋白表达与胰腺癌TNM分期及淋巴结转移相关(P=0. 001,P=0. 009)。Beclin-1蛋白表达与胰腺癌TNM分期相关(P=0. 011)。经Spearman秩相关检验,LC3与Beclin-1蛋白在胰腺癌中的表达呈正相关(r=0. 289,P=0. 006 7)。Kaplan-Meier生存分析显示,LC3或Beclin-1蛋白高表达患者生存时间相对缩短(P=0. 001 8,P 0. 001)。Cox风险模型分析显示,临床TNM分期、淋巴结转移及LC3和Beclin-1蛋白表达与患者生存时间有关(P均0. 05),其中临床TNM分期和Beclin-1蛋白表达是影响患者生存期的独立预后因素(P0. 001,P=0. 012)。结论自噬相关基因LC3和Beclin-1在胰腺癌发生、发展中可能起重要作用,对LC3和Beclin-1蛋白表达的联合检测有助于胰腺癌的预后判断。     

存活素和尿激酶型纤溶酶原激活剂在人胰腺癌组织中的表达意义及相关性分析

目的分析存活素(Survivin)和尿激酶型纤溶酶原激活剂(u PA)在人胰腺癌中的表达及两者之间的相关性。方法采用免疫组化PV法检测原发性胰腺癌组织(63例)及癌旁非肿瘤胰腺组织(11例)中Survivin和u PA的表达,分析两者间表达的相关性及与胰腺癌临床病理特征的关系。结果 63例胰腺癌组织中Survivin和u PA阳性率分别为69.8%(44/63)、65.1%(41/63),11例癌旁非肿瘤胰腺组织中均无表达,Survivin和u PA表达呈正相关(r=0.389,P0.050),两者与胰腺癌TNM分期、分化程度及淋巴结转移均有关(P均0.05)。结论 Survivin和u PA在胰腺癌组织中的表达呈正相关,两者表达上调在胰腺癌的发生、发展、侵袭和转移中起重要作用。     

FHL1在人胰腺癌族中的表达及其与胰腺癌的侵袭及转移的相关性研究

目的:探讨FHL1蛋白在胰腺癌组织中的表达及其与胰腺癌临床病理特征的关系.方法:利用Western blot检测62例胰腺癌手术切除标本与其相对应的癌旁胰腺组织中FHL1蛋白的表达.用Log-rank检验分析FHL1蛋白表达与预后的关系.结果:FHL1的蛋白表达在胰腺癌中与对应癌旁胰腺组织相比下降明显(0.197±0.042 vs. 0.508±0.272,P<0.01).同时,FHL1在胰腺癌中的表达与临床分期、病理分级、淋巴结转移、肿瘤累及范围、远处转移均有明显差异(P<0.05),与高表达FHL1组相比,低表达FHL1组患术后生存时间明显缩短(P<0.01).结论:FHL1的异常表达很可能与胰腺癌的侵袭、转移等密切相关,而这种异常表达又影响了胰腺癌患的预后.     

MMP16在胰腺癌组织中的表达及其临床意义

目的：检测胰腺癌组织中MMP16蛋白表达情况,探讨其在胰腺癌发生、发展中的作用、及其临床意义。方法：应用免疫印迹法检测8对胰腺癌/癌旁组织中MMP16蛋白的表达情况;应用免疫组化EnVision法检测49例胰腺癌组织中MMP16蛋白的表达情况,分析其与临床病理因素的关系。结果：免疫印迹法检测显示,胰腺癌组织MMP16蛋白的相对表达量均高于相应癌旁组织(8/8);免疫组化检测显示,在胰腺癌组织中MMP16蛋白的表达率为85.7%(42/49),而在癌旁正常组织中MMP16蛋白表达率为9.1%(3/33);MMP16蛋白在癌组织中的表达率明显高于癌旁正常组织,差异有统计学意义(P<0.05)。MMP16表达与胰腺癌的组织分化程度、临床分期、淋巴结转移有关;该三因素的分组间均有统计学差异(P<0.05)。结论：MMP16在胰腺癌组织中呈高表达,因此可能在胰腺癌的发生、发展中起重要作用。     

喉鳞状细胞癌中FAK和E-cadherin的表达及意义

目的 探讨粘着斑激酶(FAK)和E-钙黏蛋白(E-cadherin)在喉鳞状细胞癌(LSCC)组织中的表达与肿瘤的病理学分级及颈淋巴结转移之间的关系.方法 应用逆转录多聚酶链反应(RT-PCR)和免疫组化sP法检测LSCC和癌旁组织中FAK和E-cadherin表达情况.结果 在癌和癌旁组织中,FAK和E-cadherin mRNA的相对表达量差异具有显著性(P<0.05),且两者的表达与LSCC的淋巴结转移相关(P<0.05).E-cadherin mRNA相对表达量与肿瘤病理学分级相关(P<0.01).在癌及癌旁组织中FAK和E-cadherin的蛋白表达差异具有显著性(P<0.01),并且与颈部淋巴结转移有关(P<0.05);E-cadherin蛋白表达与肿瘤病理学分级相关(P<0.05).FAK与E-cadherin在mRNA水平或蛋白水平其表达呈负相关(r=-0.287,P<0.05;r=-0.287,P<0.05).结论 FAK的表达增高与E-cadherin的表达降低可能参与了LSCC的发生过程,是LSCC恶性程度及侵袭转移的重要标志物,对预测LSCC预后具有重要意义.     

CCR1在鼻咽癌中的表达及其临床意义

目的 研究趋化因子受体1 (CC chemokine receptor 1,CCR1)在鼻咽癌中的表达及其临床意义.方法 运用免疫组化染色法及荧光定量PCR方法检测71例鼻咽癌组织及71例癌旁组织中CCR1的表达水平,分析CCR1表达与鼻咽癌患者临床病理特征之间的关系.结果 免疫组化结果显示,CCR1在鼻咽癌组织中的阳性率为77.5％(55/71),在癌旁组织中的阳性率为21.1％ (15/71),鼻咽癌组织中CCR1表达水平显著高于癌旁组织(P＜0.05);荧光定量PCR检测结果显示,在鼻咽癌组织中CCR1 mRNA的表达水平显著高于癌旁组织,差异具有统计学意义(P＜0.05).CCR1的表达与鼻咽癌患者的年龄、性别无显著相关性,而与患者的临床分期、T分期、分化程度、淋巴结转移呈正相关关系.结论 CCR1在鼻咽癌的发生发展中可能起到癌基因的作用,CCR1表达水平可作为判断鼻咽癌临床预后的预测指标.     

Enhanced HIV-1 replication by chemokines constitutively expressed in secondary lymphoid tissues

Persistent infection of human immunodeficiency virus (HIV) takes place in the secondary lymphoid tissues even during clinically latent stages. The CC chemokines secondary lymphoid tissue chemokine (SLC) and EBI1-ligand chemokine (ELC) are constitutively expressed in the secondary lymphoid tissues. They share CCR7 expressed on lymphocytes and mature dendritic cells and play key roles in the trafficking of these types of cells into the secondary lymphoid tissues. Here we report that growth of both X4 and R5 strains of HIV-1 in activated peripheral blood T cells was enhanced by SLC. The enhancing effect of SLC was abrogated by pretreatment of cells with pertussis toxin, indicating the involvement of signaling via a receptor coupled with a Galphai class of G-protein. Furthermore, SLC was found to enhance the promoter activity of HIV-1 LTR. These results suggest that signaling via CCR7 has a strong positive effect on HIV growth. Thus, SLC and ELC may contribute to persistent infection of HIV in the secondary lymphoid tissues by promoting viral replication in activated T cells.     

CD133与SLC7A11在NSCLC中的表达及其与病理特征的关系

目的 探讨CD133及SLC7A11在非小细胞肺癌（NSCLC）组织及邻近正常肺组织中的表达及临床意义。方法 选取2015年1月~2019年7月我院经病理科确诊的NSCLC组织标本42例,并选取病理证实无癌细胞浸润的邻近正常肺组织标本（距癌组织＞5 cm）30例,比较NSCLC组织和邻近正常肺组织中CD133和SLC7A11阳性率表达、CD133及SLC7A11阳性表达与临床病理的关系及其在NSCLC组织中共表达关系。结果 NSCLC组织中CD133、SLC7A11阳性率为57.14%、64.29%,高于邻近正常肺组织的10.00%、6.67%,差异有统计学意义（P＜0.05）。不同分化程度、淋巴结转移、TNM分期癌组织中CD133、SLC7A11阳性表达比较,差异有统计学意义（P＜0.05）;不同性别、年龄、组织学类型癌组织中的CD133、SLC7A11阳性表达比较,差异无统计学意义（P＞0.05）。24例CD133阳性表达中,有21例SLC7A11阳性表达;18例CD133阴性表达中,有12例SLC7A11阴性表达,CD133、SLC7A11在NSCLC中的表达呈正相关（r=0.532,P＜0.05）。结论 CD133、SLC7A11在NSCLC中的高表达与癌组织的恶性行为及患者较差预后密切相关,对NSCLC早期诊断和靶向治疗具有重要意义。     

多器官功能障碍综合征小鼠肺间质树突状细胞的病理学观察

目的探讨肺间质树突状细胞在多器官功能障碍综合征（MODS）免疫紊乱及脏器损伤机制中的变化与作用。方法C57BL／6小鼠腹腔注射酵母多糖复制MODS模型,分为正常、3—6h（致伤早期）、12～48h[失控性全身炎性反应（SIRS）期]、5～7d（恢复期）和10～12d（MODS期）组。光镜与电镜观察各组小鼠肺及间质树突状细胞的病变;运用免疫组织化学方法检测间质树突状细胞表面标记物CD11c和CD205,共刺激分子CD80和CD86在肺中的表达水平;逆转录-聚合酶链反应法检测趋化因子SLC及其受体CCR7在肺中的表达情况;流式细胞术检测MODS各期小鼠外周血CD4^＋与CD8^＋的T淋巴细胞数量与比值。结果致伤早期,肺间质树突状细胞显著增生,共刺激分子CD80和CD86低水平表达,趋化因子SLC及其受体CCR7在肺组织中表达水平开始上升,外周血T淋巴细胞CD4^＋／CD8^＋比值下降;SIRS期,间质树突状细胞继续增生,CD80和CD86标记阳性细胞数显著上升（与正常组比较均P〈0．01）,SLC与CCR7在肺组织中表达明显高于正常组（均P〈0．01）,外周血T淋巴细胞CD4^＋／CD8^＋比值明显下降（与正常组比较P〈0．01）;MODS期,肺间质树突状细胞高度增生,但CD80和CD86表达显著减少（与SIRS期比较P〈0．01）,肺组织中SLC表达水平继续上升,而CCR7表达水平明显下降（与SIRS期比较P〈0．01）,外周血T淋巴细胞CD4^＋／CD8^＋比值显著下降。结论肺间质树突状细胞在MODS中的变化可能参与并影响了MODS病程中的免疫失衡与免疫抑制过程。CCR7的表达水平可以作为估价间质树突状细胞迁移活性和机体免疫应答水平的一个指标。     

The T cell chemokine receptor CCR7 is internalized on stimulation with ELC, but not with SLC.

ELC and SLC are potent agonists for CCR7, a receptor of up-most importance for the regulation of the homing and traffic of lymphocytes into and within secondary lymphoid tissues. We have studied the effects of both chemokines on receptor re-distribution in T lymphocytes and other CCR7-bearing cells by flow cytometry and by assessing receptor mediated functions. In this paper we show that ELC and SLC differ fundamentally in the ability to induce the internalization of their receptor. ELC induced a rapid time- and concentration-dependent internalization of CCR7 and markedly decreased the ability of CCR7-bearing cells to respond to a second stimulation. No receptor internalization, by contrast, was observed on stimulation with SLC. Receptors that were internalized on stimulation with ELC were re-expressed when the cells were washed. Re-expression of receptors and consequent re-activation of the cells was prevented in the presence of ELC, but was not affected in the presence of SLC. These findings could explain how T lymphocytes that enter lymphoid tissues in response to SLC produced by high-endothelial venules can subsequently migrate in response to SLC and ELC expressed within the T cell areas.     

The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7

Secondary lymphoid-tissue chemokine, SLC, also known as exodus-2 and 6Ckine, is a novel CC chemokine with selectivity for T lymphocytes and preferential expression in lymphoid tissues. We have studied its production, receptor usage and biological activities. High levels of SLC mRNA were detected in lymph nodes, the gastrointestinal tract and several gland tissues, but no expression was found by Northern blot analysis in freshly isolated or stimulated blood monocytes and lymphocytes, or neutrophils and eosinophils. In situ hybridization revealed constitutive expression of SLC in the T cell areas and the marginal zone of follicles in lymph nodes and the mucosa-associated lymphoid tissue, but not in B cell areas or sinuses. Comparison with immunocytochemical staining showed similarity between the in situ expression of SLC and the distribution of interdigitating dendritic cells but not with sinus-lining dendritic cells, macrophages or T lymphocytes. SLC induced chemotaxis of T lymphocytes and its activity increased considerably when the cells were conditioned with IL-2 or phytohemagglutinin (PHA). Under optimal conditions SLC had unusually high efficacy and induced the migration of up to 50 % of input T lymphocytes. SLC also induced Ca²⁺ mobilization in these cells. Similar responses were obtained with EBI1 ligand chemokine (ELC), and sequential stimulation with both chemokines led to cross-desensitization, suggesting that SLC acts via the ELC receptor, CCR7. This was confirmed using murine pre-B cells stably transfected with CCR7 which bound SLC with high affinity and showed chemotaxis and Ca²⁺ mobilization in response to both SLC and ELC. In T lymphocytes PHA and IL-2, which enhanced chemotactic responsiveness, also markedly enhanced CCR7 expression. In contrast to all known chemokine receptors, up-regulation of CCR7 by IL-2 was transient. A maximum was reached in 2 – 3 days and expression returned to initial levels within 8 – 10 days. The present study shows that SLC is constitutively produced within the T cell areas of secondary lymphoid organs and attracts T lymphocytes via CCR7.     

Augmented expression of secondary lymphoid tissue chemokine and EBI1 ligand chemokine in Crohn's disease

BACKGROUND: A dominant T helper type 1 (Th1) immune response is thought to be involved in Crohn's disease (CD). SLC/CCL21 and ELC/CCL19, chemokines that regulate T cell homing and promote recirculating T and dendritic cell (DC) interactions, help control antigen specific T cell responses. AIMS: To investigate the Th1 response and SLC and ELC in CD pathogenesis. METHODS: Surgically resected intestine and mesenteric lymph nodes (MLNs) from controls and patients with CD and ulcerative colitis (UC) were investigated. CD3, CD83, HECA452, VEGFR3, SLC, ELC, and CCR7 expression was studied immunohistochemically. CCR7 mRNA was quantified using real time RT-PCR. RESULTS: ELC was almost undetectable in intestinal samples. SLC was found sporadically in lymphoid follicles, lymphoid aggregate venules, and lymphatic vessels. In MLNs, SLC was highly expressed in high endothelial venules (HEVs), lymphatic vessels, and stromal DCs, predominantly in T cell areas. ELC was highly expressed in mature DCs. There were significantly more SLC positive HEVs and ELC positive mature DCs, important components of T cell areas, in CD. SLC, ELC, and CCR7 mRNA was significantly higher in CD MLNs compared with UC. CD MLNs had increased expression of SLC and ELC, mainly in HEVs, mature DCs, and lymphatic vessels, inducing T cell hyperplasia. CCR7 mRNA was increased in T cell areas. CONCLUSION: The dominant Th1 immune response is facilitated by interaction of SLC positive HEVs/lymphatic vessels, ELC positive mature DCs, and CCR7 positive T cells in hyperplastic T cell areas. In CD, memory T cells and mature DCs may home to MLN.     

哮喘豚鼠模型肺和骨髓中CCR3及CD34的表达及意义

目的:观察哮喘豚鼠肺和骨髓组织CCR3及EOS不同时相表达的变化, 探讨哮喘发病的可能机制.方法:用卵白蛋白(OVA)和生理盐水致敏法制备豚鼠哮喘和对照模型, 分为正常对照组(N)及哮喘组(A、B、C、D、E), 每组8只, 于激发后30 min, 6 h, 12 h, 24 h, 48 h处死, 瑞氏染色计数骨髓涂片和外周血涂片中EOS比例, 免疫组织化学技术检测骨髓中CCR3及CD34蛋白的表达;制备豚鼠肺组织病理标本, 苏木精-伊红染色, 免疫组化检测肺组织中CCR3和CD34的表达.结果:(1)哮喘组骨髓和外周CCR3与CD34及EOS表达明显增加;(2)OVA激发后, 骨髓和外周CCR3、CD34及EOS表达:30 min变化不明显(肺内CD34表达增加), 6 h(肺内CD34表达下降)、12 h达到峰值, 24 h开始下降, 48 h恢复正常水平;(3)骨髓的变化早于外周, CCR3的表达高峰早于CD34表达与EOS的增多高峰, 且CCR3、CD34和EOS互呈线性相关(肺组织内除外).结论:哮喘豚鼠肺组织和骨髓之间存在骨髓CD34 祖细胞、EOS细胞到循环再到肺组织的通路, 骨髓和肺组织CCR3表达增强, 为CD34 细胞、EOS从骨髓快速募集到肺组织提供了可能.     

Chemokine receptor CCR7 guides T cell exit from peripheral tissues and entry into afferent lymphatics

T cell circulation between peripheral tissues and the lymphoid compartment is critical for immunosurveillance and host defense. However, the factors that determine whether T cells remain in peripheral tissue or return to the circulation are undefined. Here we demonstrate that the chemokine receptor CCR7 is a critical signal that determines T cell exit from peripheral tissue. Both CCR7(-) and CCR7(+) effector T cells entered mouse asthmatic lung and while CCR7(-) T cells accumulated, CCR7(+) T cells continued to migrate into afferent lymph. Delivery of both CCR7(+) and CCR7(-) T cells directly into the airways showed that only CCR7(+) T cells exited the lung and entered draining lymph nodes. Our study establishes a molecular basis for T cell exit from peripheral tissues.     

SLC/CCR7 Stimulates the Proliferation of BMDCs by the pNF‐κB p65 Pathway

The chemokine receptor CCR7 is highly expressed in dendritic cells (DCs), T cells, and other immune effector cells. One of the high‐affinity ligand that can bind to CCR7 is the secondary lymphoid tissue chemokine (SLC). The SLC/CCR7 axis plays an important role in the immune system by inducing the chemotaxis and migration of immune effector cells. In this study, we examined the effect of SLC at different concentrations (0, 50, 100, 200, 300, and 400 ng/mL) on the proliferation of bone‐marrow‐derived dendritic cells (BMDCs). ELC (CCL19), another high‐affinity ligand for CCR7, was used as the control at the same time. We found that SLC directly stimulated the proliferation of BMDCs and enhanced the antigen‐presenting function and CCR7 expression. Western blot analysis showed that pNF‐κBp65 was involved in this mechanism. We also found that the NF‐κB inhibitor PDTC could specifically block the proliferation and CCR7 expression of BMDCs induced by SLC or ELC (200 ng/mL). The results suggested that there were cross‐talk signals between the chemotaxis and proliferation of BMDCs involving the SLC/CCR7 axis. Anat Rec, 2010. © 2009 Wiley‐Liss, Inc.     

CCL21‐expression and accumulation of CCR7+ NK cells in livers of patients with primary sclerosing cholangitis

The pathogenesis of primary sclerosing cholangitis (PSC), an autoimmune liver disease, remains unknown. The aim of this study was to characterize peripheral blood and intrahepatic NK cells from patients with PSC. Peripheral blood samples from patients with PSC, other autoimmune liver diseases, and from healthy control individuals were used, as well as liver tissues from PSC patients undergoing liver transplantation. Multiparameter flow cytometry showed that peripheral blood NK cells from PSC patients were significantly enriched for CCR7⁺ and CXCR3⁺ cells, and CCR7⁺ but not CXCR3⁺ cells were also significantly increased within intrahepatic NK cells. PSC patients undergoing liver transplantation furthermore had significantly higher plasma levels of the CCR7‐ligand CCL21, and the CXCR3‐ligands CXCL10 and CXCL11, and significantly higher levels of CCL21, but not CXCL10, were detected in liver tissues. CCR7⁺ and CXCR3⁺ NK cells from PSC patients exhibited significantly higher functional capacity in peripheral blood, but not liver tissues, consistent with chronic activation of these NK cells in the inflamed liver. These data show that PSC is characterized by intrahepatic CCL21 expression and accumulation of CCR7⁺ NK cells in the inflamed liver tissue.