人静脉移植物中MCP-1的表达

目的：探讨人静脉移植物中单核细胞趋化蛋白-1（MCP-1）的表达及其与巨噬细胞浸润的关系。方法：应用免疫荧光组织化学技术对30个静脉移植物再塞标本中MCP-1、CD68（巨噬细胞的标记物）、CD3l（内皮细胞的标记物）的表达进行了检测，用激光共聚焦显微镜拍片，图片用Silicon Graphics Octane进行处理。结果：在正常静脉血管中，MCP-1表达很弱；外膜中有少量CD68免疫阳性细胞，中膜和内膜中少见；CD31免疫阳性细胞仅在血管腔内皮细胞和外膜小血管中可见。在病变静脉血管，MCP-1在内皮细胞、平滑肌细胞中的表达呈强阳性；CD68免疫阳性细胞在外膜、中膜和内膜均可见到；CD31免疫阳性细胞不仅出现在血管腔内皮细胞和外膜小血管内皮细胞，且在中膜小血管内皮细胞也大量出现。免疫双重染色显示内皮细胞和巨噬细胞均表达MCP-1。结论：人静脉移植物MCP-1的表达上调，且和巨噬细胞的浸润关系密切，提示MCP-l对静物移植物炎症细胞的浸润及新内膜的形成有非常重要的作用。     

树突状细胞表型抗原在人卵巢癌组织中的表达

目的：观察人卵巢癌中CD1c、S－100阳性细胞数和表达强度的变化，探讨其与卵巢癌发生发展及预后的关系。为卵巢癌的生物治疗提供实验依据。方法：应用ABC免疫组化技术和图像分析法对31例卵巢癌标本进行检测。结果：在卵巢癌中CD1c S－100阳性细胞数与正常卵巢组织比较明显减少（P＜0．01），且其表达强与正常卵巢组织比较明显减弱（P＜0．01）。结论：树突状细胞表型抗原在人卵巢癌组织中的表达总量下降，树突状细胞在抗卵巢癌的免疫反应中起重要作用。     

树突状细胞在子宫内膜异位症内膜组织中的变化

目的检测不成熟树突状细胞(im DCs)及成熟树突状细胞(m DCs)的标记物CD1a和CD83在子宫内膜异位症(EMS)内膜组织中的表达,探讨不同发育阶段的DCs在子宫内膜异位症发生发展中的作用。方法选取病理检查确诊的"巧克力囊肿"患者30例,分别取其异位内膜组织(异位内膜组)和在位内膜组织(在位内膜组),同时选取30例非内异症内膜组织为对照组。免疫组织化学法检测CD1a、CD83蛋白表达和分布,免疫印迹法检测CD1a、CD83蛋白表达量。结果 CD1a和CD83阳性细胞均分布于固有层基质细胞间及血管周围;CD1a蛋白在对照组、在位内膜组、异位内膜组表达依次升高,组间比较差异均有统计学意义(P0.01);CD83蛋白在对照组、在位内膜组、异位内膜组表达依次减少,差异均有统计学意义(P0.01)。结论子宫内膜异位症患者子宫内膜局部im DCs增多、m DCs减少,可能在子宫内膜异位症中发挥作用。     

人宫颈上皮内瘤变和浸润癌组织中树突状细胞及T细胞的免疫组织化学定量分析

目的 研究人宫颈上皮内瘤变和浸润癌组织中树突状细胞和T细胞的数量、分布变化,为人宫颈癌的诊断和生物治疗提供实验依据.方法 采用免疫组织化学和图像分析技术,测定人宫颈上皮内瘤变、宫颈浸润癌和正常宫颈组织中树突状细胞表型抗原CD1a、S-100及T细胞表面分化抗原CD3、CD8阳性细胞的数量、分布和表达强度.结果 与人正常宫颈组织比较,宫颈上皮内瘤变中CD1a 、S-100 、CD3 、CD8 细胞数量增多(P＜0.05),与组织分级呈正相关(P＜0.05),抗体表达强度增高;宫颈浸润癌中4种抗体阳性细胞数量减少,与临床分期呈负相关(P＜0.05),强度略有下降.结论 人宫颈上皮癌前病变至浸润癌变过程中树突状细胞和T细胞数量及抗体表达强度发生变化,提示宫颈病变局部的免疫功能发生了改变.     

正常皮肤中单核巨噬细胞和树枝状细胞的分布规律

目的：观察正常真皮内的单核-巨噬细胞和树枝状细胞的分布、排列规律，探讨单核-巨噬细胞在皮肤免疫防御中的作用。方法：正常皮肤8例，取面部、躯干、四肢近端、四肢远端、手掌和足跖6个部位皮肤，进行纵行与水平切片。CD1a和CD68单克隆抗体染色，观察朗格汉斯细胞（LC）和单核．巨噬细胞的分布形态和密度。结果：真皮浅层CD68阳性细胞呈网状分布，其密度为361-562个／mm^2。真皮内血管周围及附属器周围亦见CD68阳性细胞。真皮深层CD68阳性细胞多为树枝状，散在分布于粗大的胶原纤维之间。不同解剖部位真皮浅层CD68阳性细胞密度分别为：四肢远端562个／mm^2，腹部517个／mm^2，面部509个／mm^2，手掌507个／mm^2，四肢近端472个／mm^2，足跖361个／mm^2。真皮浅层CD68阳性细胞在手掌和足跖部位高于相应部位的表皮内CD1a和CD68细胞。结论：在真皮浅层形成数层单核．巨噬细胞网，此网在接近真表皮交界处较致密。真皮内单核-巨噬细胞的这种分布形式说明这些细胞在真皮内有明确的方向性，其防御的方向是穿透表皮进入真皮的入侵物。     

人卵巢上皮癌组织中树突状细胞表型抗原的免疫组织化学研究

目的：观察人卵巢上皮癌中CD1c、S－100树突状阳性细胞数和表达强度及癌局部微环境中细胞表型抗原的变化,探讨其与卵巢上皮癌发生、发展的关系,为临床生物治疗提供实验依据。方法：采用ABC免疫组织化学技术和图像分析。结果：在卵巢上皮癌中,CD1c^ 、S－100^ 细胞数明显减少,与正常卵巢组织相比较具有显著性差异,与临床分期和病理分级无关;卵巢上皮癌中D1c、S－100阳性细胞表达强度与正常卵巢组织相比较明显减弱,具有显著性差异（P＜0．01）,与临床分期和病理 分级相关。结论：人卵巢上皮癌局部微环境中,树突状细胞表型抗原表达总量下降,说明树突状细胞在抗卵巢上皮癌的免疫应答中具有重要作用。     

以皮疹为首发症状的儿童朗格汉斯细胞组织细胞增生症19例临床病理分析

目的探讨以皮疹为首发症状就诊的朗格汉斯细胞组织细胞增生症(Langerhans-cell histiocytosis,LCH)的临床病理特点,为其早期准确诊断提供有益的帮助。方法收集天津市儿童医院2012年5月～2017年3月以皮疹为首发症状就诊的19例LCH,所有病例均采用直径4.5 mm的皮钻于病变典型部位行皮肤活检,活检标本行常规HE染色及CD1a、S-100、Langerin、CD68、CD3、CD20、CD117免疫组化染色。结果皮疹大体形态多样,镜下病变大部分位于真皮内(10/19),呈灶状或弥漫分布,8例可见表皮侵犯,1例仅在表皮内形成表皮内疱,疱内可见瘤细胞,真皮内未见瘤细胞。典型的肿瘤细胞大小较一致,细胞界限不清,胞质略呈嗜酸性,核不规则、凹陷,可见核沟(15/19),部分病例肿瘤细胞形态不典型,未见明显核沟。免疫表型:CD1a、Langerin、S-100均阳性(19/19),CD68部分阳性(16/19),病灶中或病灶周围均可见CD3阳性的T淋巴细胞,CD117阴性。结论儿童LCH皮疹形态多样,且常为该疾病的最早期表现,提高对LCH皮疹的认识,及时行皮肤活检及免疫组化染色,对儿童LCH的早期诊断和治疗具有重要意义。     

低浓度脂多糖加速大鼠颈动脉球囊损伤后新生内膜的形成

目的：探讨低浓度脂多糖（LPS）刺激机体免疫系统对血管损伤后加速血管新生内膜增生的影响。方法：选用健康Wistar大鼠，静脉注入LPS后，行颈动脉球囊损伤术，建立血管内膜损伤模型。采用免疫荧光或组织化学染色观察内膜增生变化。Western blot 分析损伤组织特异性平滑肌细胞标志物和细胞凋亡表达。用ELISA测定血清白介素-1β(IL-1β)含量和流式细胞术分析CD14阳性细胞表达水平。结果：每只鼠注入LPS(50 ng)后循环血中单核细胞和IL-1β水平显著升高。血管损伤7 d后中膜平滑肌细胞增殖, 转化为合成表型，新生内膜逐渐形成，随时间延长，内膜增生加速，内膜厚度由(151.2±14.5)μm2增至(173.9±15.3)μm2。免疫荧光染色观察到增殖细胞核抗原及核因子-κB分别定位于新生内膜和外膜。Western blot分析显示新生内膜形成早期LPS组平滑肌特异性标志蛋白α-肌动蛋白多于对照组，caspase-3表达持续上调，细胞凋亡多于对照组。结论：炎症介质LPS刺激全身免疫系统导致血管损伤后新生内膜暂时性增生，表明炎症介质可以加剧血管损伤后再狭窄的形成。     

草分支杆菌对人脐血树突状细胞体外扩增的影响

背景：树突状细胞因其强大的抗原提呈能力而在机体抗肿瘤作用的中心地位逐渐受到重视,但如何能有效获得足够数量有功能的树突状细胞成为目前研究的重点,尤其是有关低毒免疫调节剂的报道较少。 目的：观察草分支杆菌F.U.36(乌体林斯,Utilins)对人脐血来源树突状细胞体外扩增的影响。 方法：应用Ficoll-Hypaque法分离人脐血单个核细胞,分别用乌体林斯,细胞因子(重组人粒细胞-巨噬细胞集落刺激因子+重组人肿瘤坏死因子α+重组人白细胞介素4),细胞因子联合乌体林斯进行干预,并以RPMI-1640培养液诱导培养人脐血单个核细胞作为对照组,诱导培养树突状细胞,并于倒置显微镜下观察其生长情况及形态。培养第9天,采用流式细胞仪检测各组人树突状细胞特异性表型CD1a及MHC-Ⅱ分子HLA-DR的变化,并将细胞涂片行瑞氏-姬姆萨染液染色,油镜下观察摄片。 结果与结论：除对照组外,实验各组均得到高表达CD1a及HLA-DR的典型树突状细胞。乌体林斯组CD1a及HLA-DR阳性细胞比例亦明显高于对照组而低于细胞因子组 (P < 0.05),联合组HLA-DR阳性细胞比例高于细胞因子组(P < 0.05)。结果提示,草分支杆菌F.U.36(乌体林斯)不仅能促进脐血树突状细胞体外扩增,还能协同细胞因子促进树突状细胞成熟。     

胎儿子宫内膜内分泌细胞的免疫组化观察

目的：观察胎儿子宫内膜内分泌细胞的发育规律、形态特征及含物，探讨其生物学意义。方法：12～39w胎儿子宫内膜20例，采用嗜铬素A免疫组化染色标记内分泌细胞；血清素，生长抑素及胃泌素释放肽的免疫组化染色，观察胎儿子宫内膜内分泌细胞的内含物。结果：最早在16w子宫膜内膜上皮出现CgA阳性细胞，分布在子宫上皮及腺上皮，以靠近基底处较多。各胎龄组子宫内膜均未见血清素、生长抑素及胃泌素释放肽阳性细胞。结论：胎儿子宫内膜与成人子宫内膜的内分泌细胞在分布、数量和类型上存在差异。内分泌细胞在胚胎早期出现，提示内分泌细胞对子宫内膜的发育具有特殊意义。     

新疆维吾尔族妇女宫颈上皮内瘤变及宫颈癌中树突状细胞的检测及意义

目的探讨树突状细胞在新疆维吾尔族妇女宫颈上皮内瘤变(cervical intraepithelial neoplasia,CIN)及宫颈癌中的检测及意义。方法 将HLA-DR、CD1a、S-100蛋白作为DC特异性标记物,采用免疫组织化学方法对20例慢性宫颈炎、70例CIN(CINⅠ25例、CINⅡ25例、CINⅢ20例)以及40例浸润性宫颈鳞癌组织标本中DC的分布和表达进行检测。结果 S-100、CD1a和HLA-DR阳性表达率依次为浸润性宫颈鳞癌(65.00%,55.00%,62.50%)>CIN(50.00%,44.29%,40.00%)>慢性宫颈炎(30.00%,20.00%,25.00%),差异具有统计学意义(P=0.035,P=0.037,P=0.012),S-100、CD1a和HLA-DR分布于癌组织及癌巢附近的间质中。在宫颈各组织中,CD1a与S-100蛋白表达呈正相关(r=0.330,P=0.000);CD1a与HLA-DR表达也呈正相关(r=0.267,P=0.002);而S-100蛋白与HLA-DR表达没有相关性(r=0.065,P=0.461)。结论人宫颈上皮内瘤变至浸润癌变过程中树突状细胞特异性标记物S-100、HLA-DR、CD1a表达强度发生变化,提示宫颈病变局部的免疫功能发生了改变。     

Activated myeloid dendritic cells accumulate and co-localize with CD3+ T cells in coronary artery lesions in patients with Kawasaki disease

Emerging evidence implicating the participation of dendritic cells (DCs) and T cells in various vascular inflammatory diseases such as giant cell arteritis, Takayasu's arteritis, and atherosclerosis led us to hypothesize that they might also participate in the pathogenesis of coronary arteritis in Kawasaki disease (KD). Coronary artery specimens from 4 patients with KD and 6 control patients were obtained. Immunohistochemical and computer-assisted histomorphometric analyses were performed to detect all myeloid DCs (S-100(+), fascin(+)), all plasmacytoid DCs (CD123(+)) as well as specific DC subsets (mature myeloid DCs [CD83(+)], myeloid [BDCA-1(+)] and plasmacytoid DC precursors [BDCA-2(+)]), T cells (CD3(+)), and all antigen-presenting cells (HLA-DR(+)). Co-localization of DCs with T cells was assessed using double immunostaining. Significantly more myeloid DCs at a precursor, immature or mature stage were found in coronary lesions of KD patients than in controls. Myeloid DC precursors were distributed equally in the intima and adventitia. Mature myeloid DCs were particularly abundant in the adventitia. There was a significant correlation between mature DCs and HLA-DR expression. Double immunostaining demonstrated frequent contacts between myeloid DCs and T cells in the outer media and adventitia. Plasmacytoid DC precursors were rarely found in the adventitia. In conclusion, coronary artery lesions of KD patients contain increased numbers of mature myeloid DCs with high HLA-DR expression and frequent T cell contacts detected immunohistochemically. This suggests that mature arterial myeloid DCs might be activating T cells in situ and may be a significant factor in the pathogenesis of coronary arteritis in KD.     

Subset of Vascular Dendritic Cells Transforming into Foam Cells in Human Atherosclerotic Lesions

It has been previously demonstrated that S-100 positive vascular dendritic cells are involved in human atherosclerosis and they usually show a low level of accumulation of lipids in their cytoplasm, even though they located among foam cells and cellular debris in atherosclerotic lesions. During ongoing immunohistochemical investigations, however, we have found that a few S-100 positive cells exhibited a foam cell appearance. Therefore, we undertook an electronmicroscopic examination to see if any foam cells exhibit the distinctive features of vascular dendritic cells such as the presence of dense granules and a tubulovesicular system uniquely found in well differentiated dendritic cells. Foam cells exhibiting the typical characteristics of vascular dendritic cells were indeed found. Their cytoplasm contained a large number of lipid vacuoles and cisterns of the tubulovesicular system as well as dense granules which, in contrast to lysosomes present in macrophages, did not transform into phagolysosomes. The formation of a central lamina inside cisterns of the tubulovesicular system was also detected. These pentalaminal structures, comprised of two parallel limiting membranes and a central lamina, are similar to the Birbeck granules present in human epidermal Langerhans cells. From our present observations we speculate that the defense mechanisms against extensive lipid accumulation may be broken in some vascular dendritic cells, causing them to transform into foam cells.     

冠状动脉外膜炎症在动脉粥样硬化病灶形成中的作用

目的：探讨动脉外膜炎症诱发载脂蛋白E基因剔除（apoE-/-）小鼠冠状动脉粥样硬化病灶发生的机制。 方法： 取apoE-/-小鼠心脏做连续切片，选择冠状动脉外膜有炎性细胞浸润的3类部位代表粥样硬化病灶形成过程中的3个阶段：①未发现粥样硬化病灶；②有直接从主动脉延伸的病灶顶端和③成熟粥样硬化病灶的冠状动脉。分别采用HE染色、Movat染色、免疫组化和透射电镜方法鉴定3个病变阶段的冠状动脉外膜中炎细胞类型。 结果： ①未发现粥样硬化病灶；②有直接从主动脉延伸的病灶顶端和③成熟粥样硬化病灶的冠状动脉外膜分别以巨噬细胞、中性粒细胞和淋巴细胞浸润为主，其构成比分别为60.00%、57.65%和66.67%，各组构成比分别与其它两组比较均有显著差异（P<0.01）。 结论： 动脉外膜炎症可能是诱发动脉粥样硬化发生的早期事件之一，ApoE-/-小鼠冠状动脉粥样硬化病灶形成过程中，动脉外膜经历了一个从急性炎症到慢性炎症的过程。     

Ultrastructural identification of cells with dendritic cell appearance in atherosclerotic aorta of apolipoprotein E deficient mice

The present electron microscopic study was undertaken to see whether cells with a dendritic cell appearance accumulate in atherosclerotic lesions of apolipoprotein E (apoE) deficient mice. Atherosclerotic aortas from 7 eight-month old apoE deficient mice were examined. In atherosclerotic plaques as well as in the underlying media and adventitia, cells with a dendritic cell appearance including the presence of a unique tubulovesicular system were detected. The tubulovesicular system was most hypertrophied in their cellular processes where the continuous cisterns sometimes formed circular structures. The cells containing the tubulovesicular system lacked lysosomes and phagolysosomes and their cytoplasm was free of lipid inclusions. The present observations suggest that dendritic cells are involved in apoE deficient mouse atherosclerosis. ApoE deficient mice might be a useful model for investigating functions of dendritic cells in atherogenesis.     

Activation of adventitial fibroblasts contributes to the early development of atherosclerosis: a novel hypothesis that complements the "Response-to-Injury Hypothesis" and the "Inflammation Hypothesis"

The role of the adventitia in vascular function and vascular lesion formation has been largely ignored. This article introduces the hypothesis that the activation of the adventitia, specifically the fibroblasts, contributes to the formation of intimal atherosclerotic lesions. The evidence for this hypothesis includes: (a) the early proliferative changes seen in fibroblasts found in the adventitia; (b) the increase and the alteration of extracellular matrix deposition in the adventitia; (c) fibroblast differentiation into myofibroblasts and migration into the intima; and (d) fibroblast synthesis and release of cytokines that have potent effects on neighboring smooth muscle and endothelial cells prior to intimal lesion formation. In conclusion, the activation of adventitial fibroblasts is a key regulator of vascular function and structure from the "outside-in" and contributes to the development of atherosclerotic lesions. The outer location of the adventitia makes it a suitable location for drug delivery and gene therapy aimed at preventing and treating atherosclerosis.     

Rupture of the thyrocervical trunk branch from the subclavian artery in a patient with neurofibromatosis: a case report.

BACKGROUND: Vascular involvement in neurofibromatosis type 1 (NF1) is well recognized; however, rupture of extracranial arteries rarely occurs. We present a case of NF1 with rupture of the thyrocervical trunk, which branched from the right subclavian artery. A 76-year-old woman who has numerous café-au-lait spots and soft tumors of the skin manifested a sudden swelling of her neck accompanied with increasing pain. Radiological examinations revealed bleeding from the artery. METHODS: Histological and immunohistochemical examinations were carried out using tissues that contained the affected vessel. RESULTS: Proliferation of spindle cells positive for S-100 protein was seen in the adventitia of the ruptured vessel. Intimal thickening by proliferation of fibromuscular cells was also evident with irregularity of the media. CONCLUSIONS: These findings suggest that the artery was disrupted by NF in the vascular wall. It is considered that NF in the arterial wall causes dysplasia of the smooth muscle layer in the intima and media and leads to fragility of the vessel. Twelve cases, including the present case, with rupture of extracranial arteries in NF1 have been reported in the past 10 years; two thirds of these occurred in extravisceral sites in which there is a good deal of physical movement. This suggests that a physiological factor is one of the triggers for arterial rupture, which occurs under a background of vascular fragility in NF1.     

The interactions between human dendritic cells and microbes; possible clinical applications of dendritic cells

The dendritic cells comprise several subsets that induce and regulate the immune responses against foreign and self-antigens, and that can therefore function as initiators of protective immunity and inducers of central or peripheral tolerance. The different subpopulations of dendritic cells interact with and also influence other cell populations of the immune system, such as T and B lymphocytes and natural killer cells. The factors that determine the given dendritic cell functions depend on the state of maturation and the local microenvironment. The interactions between dendritic cells and microorganisms are rather complex, but progress in the past few years has shed light on several aspects of these interactions. This review lays emphasis on the interactions between human dendritic cells, important components of the intima of arterial specimens at areas predisposed to atherosclerotic lesions, and Chlamydia pneumoniae and cytomegalovirus, the human pathogens most strongly implicated in the development of atherosclerosis. In addition, several examples of the potential clinical applications of dendritic cells are described.Received 13 January 2004; accepted by A. Falus 22 March 2004     

Inner layer infarction of the coronary artery wall due to coronary thrombosis

Cross sections of 112 coronary artery segments from 65 human hearts with coronary thromboses were investigated after postmortem coronary angiography. In almost all cases the inner layers of coronary artery walls adjacent to the obstructing thrombi or to parietal thrombi were infarcted. These infarctions followed nearly the same course as classical infarctions. From 13 hearts with segments occluded by thrombi but without atherosclerotic lesions, 19 specimens were found suitable for quantitative investigations. The 2 segments with the thinnest intima were lacking in inner layer infarctions. The other 17 specimens contained areas of inner layer necrosis of increasing diameter, depending on the thickness of the wall. In each case the media was completely preserved. The mean thickness of the noninfarcted wall tissue was 190+/-28 micro m. This noninfarcted wall tissue was supplied by vasa vasorum in the adventitia located at an average distance of approximately 40 micro m from the media. The knowledge of the supplying areas of the vasa vasorum could help us understand the pathogenesis of necroses in atherosclerotic plaques.