Murine epidermal Langerhans cells do not express inducible nitric oxide synthase

In Leishmania-infected macrophages (MΦ), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide synthase (iNOS) is critical for the killing of the intracellular parasites. We have recently shown that, in addition to MΦ, epidermal Langerhans cells (LC) can phagocytose Leishmania major, but they do not allow parasite replication. Therefore, we analyzed whether LC and MΦ display the same leishmanicidal effector mechanism. Unlike MΦ, stimulation of unselected epidermal cells with interferon-γ/lipopoly-saccharide did not lead to the release of nitric oxide (NO), and inhibition of NO production had no effect on the rate of infection of LC. iNOS mRNA was clearly detectable in MΦ as well as unselected epidermal cells (the majority of which consists of keratinocytes) after stimulation with different cytokines. In contrast, pure LC obtained by single-cell picking from cytokine-activated or L. major-infected epidermal cells did not express iNOS mRNA. Addition of the NO donor S-nitroso-N-acetylpenicillamine to already-infected LC did not alter their rate of infection, indicating that LC do not utilize exogenous NO for the control of intracellular Leishmania. These results suggest that in the L. major-infected skin, activated MΦ and keratinocytes, but not LC have the ability to express iNOS activity. Therefore, an as yet unidentified, NO-independent mechanism appears to be responsible for the control of parasite replication in LC.     

Basophil histamine release and lymphocyte proliferation tests in latex contact urticaria

Basophil histamine release and lymphocyte proliferation tests were examined with latex allergen prepared from surgical gloves in 15 patients with latex contact urticaria. The basophil histamine release test (BHRT) yielded positive results in 13/14 (93%) patients, whereas commercial latex RAST was positive in only 9/15 (60%) patients. Lymphocyte proliferation test (LPT) was positive in 3/15 (20%) patients, suggesting that cell-mediated immune reactions may also occur in latex allergy. However, patch tests to latex were negative and neither were epidermal Langerhans cells able to present latex antigen to T lymphocytes in vitro.     

胰岛的血液引流与胰腺外分泌的机能和临床意义

目的　研究胰岛的血液引流与胰腺外分泌的机能联系与临床意义。方法　运用微血管树脂 /墨汁灌注扫描电镜 /光镜观察法、保留动态及组织信息在静态样本的微循环观察法、FITC标记红细胞 (FITC- RBC)荧光活体显微镜观察法以及计算机图像处理微血管三维重建法 ,对 11例男性尸体、40只猴、2 4只狗、62只鼠、2 4只兔的胰岛血液引流通道与胰腺外分泌腺泡的关系进行了系统研究。结果　不同动物的内分泌胰岛血液主要经胰岛的三种类型输出血管引流至不同的外分泌腺泡区域 ,灵长类的部分胰岛血液还引流至邻近的小胰岛 ,研究者根据胰岛引流系统的特征对其进行了分类及命名 :1连续型引流系统 ,所有胰岛具有这类引流 (输出 )管道 ,其管径细 ,行程短、引流至胰岛周围的腺泡毛细血管区域。 2聚合型引流系统 ,为部分胰岛所有 ,其管径粗、行程长 ,引流至远离胰岛的腺泡毛细血管区域。 3跨越型引流系统 ,为部分胰岛所有 ,其输出管道越过小叶间隔引流至另一胰腺小叶的腺泡毛细血管区域 ,而这一小叶往往没有胰岛存在。 4胰岛 -胰岛型引流系统 ,灵长类部分胰岛的血液通过胰岛 -胰岛型引流通道回流至邻近的小胰岛。结论　胰岛具有完善联系外分泌腺泡的引流系统 ,提示含有高浓度胰岛内分泌激素的胰岛血液可能对外分泌腺泡的机能     

Clinical use of donation after circulatory death pancreas for islet transplantation

Due to a shortage of donation after brain death (DBD) organs, donation after circulatory death (DCD) is increasingly performed. In the field of islet transplantation, there is uncertainty regarding the suitability of DCD pancreas in terms of islet yield and function after islet isolation. The aim of this study was to investigate the potential use of DCD pancreas for islet transplantation. Islet isolation procedures from 126 category 3 DCD and 258 DBD pancreas were performed in a 9-year period. Islet yield after isolation was significantly lower for DCD compared to DBD pancreas (395 515 islet equivalents [IEQ] and 480 017 IEQ, respectively; p = .003). The decrease in IEQ during 2 days of culture was not different between the two groups. Warm ischemia time was not related to DCD islet yield. In vitro insulin secretion after a glucose challenge was similar between DCD and DBD islets. After islet transplantation, DCD islet graft recipients had similar graft function (AUC C-peptide) during mixed meal tolerance tests and Igls score compared to DBD graft recipients. In conclusion, DCD islets can be considered for clinical islet transplantation.     

尖锐湿疣皮损中朗格汉斯细胞的变化

目的了解尖锐湿疣(CA)皮损中朗格汉斯细胞(LC)的变化。方法采用免疫组化法对34例CA皮损进行LC染色,光镜下观察其形态和数量变化,并对其中6例标本行电镜观察。结果与正常皮肤相比,CA皮损表皮内LC分布不规则,少见典型的树突状细胞,细胞突明显减少、缩短或消失,半定量计数显示CA皮损中LC为(13.15±9.42)个,较正常明显降低(P<0.01)。超微结构表明LC中的特征性结构———朗格汉颗粒(LG)不仅数目减少,而且形态也不典型。结论CA皮损中LC形态及数量均发生变化,可能在CA的发病中起着一定作用。     

人胰岛微血管和A细胞的微机三维重建

采用微机辅助三维重建的方法重建了人胰岛的微血管的A细胞，结果表明，所使用的软件重建速度快，图像速真，清晰度高，视觉效果好，可对重建物体进行多角度，多轴旋转，也可进行任何部位的切割，以便能进一步了解胰岛内各结构的详细情况，为进一步研究胰岛内微血管和细胞的立体位置关系提供方法学基础。     

The microanatomy of canine islets of Langerhans: implications for intra-islet regulation

Summary In recent years models for the internal (intra-islet) regulation of hormone secretion have been proposed to explain how different islet cells might regulate each other by means of their respective secretory peptides. Models that emphasize the importance of a directed intra-islet blood flow and sequence of perfusion of islet cells rely on a certain type of islet microanatomy and vascular supply. The experimental studies underlying these models have partly been performed in dogs. To extend the incomplete morphological knowledge of the canine endocrine pancreas both canine islets of Langerhans and extrainsular cells have been analysed in immunostained serial semithin (0.5 m) sections. In addition to their occurrence within islets of Langerhans, all endocrine cell types are also found at extrainsular sites (about 9% of all endocrine cells) where they are distributed in different quantities among the epithelial lining of exocrine acini or excretory ducts and the connective tissue. There are continuous transitions from single extrainsular cells to small mono-and polycellular cell groups to islets. In a comprehensive analysis of whole islets, including computer-assisted three-dimensional reconstructions, the size, shape and vascularization of the islets as well as their cellular composition and the microtopology of islet cells have been studied. We have found marked intra-and inter-islet heterogeneities of the parameters investigated that are not compatible with concepts of a uniform and directed vascular perfusion of the various islet cell populations. Instead, their paracrine regulation may occur primarily via hormonal secretion into the intercellular spaces or vascular hormonal delivery to adjacent cells.     

Concordant xenotransplantation--non-vascularized pancreatic islets are more difficult to regraft than the vascularized heart

We have previously demonstrated that it is possible to perform retransplantation of a xenogeneic heart (mouse-to-rat) using cyclosporine A as monotherapy, provided that the first heart is transplanted under a short course of deoxyspergualin (DSG). If DSG is omitted, the first heart is rejected within four days and the second heart succumbs to hyperacute rejection within minutes. A mouse heart as first graft does not protect a consecutive pancreatic islet graft, although the heart continues to function after rejection of the cellular graft. One explanation for this discrepancy may be the fact that cellular grafts, as pancreatic islets, lack an endothelial lining. We have, therefore, further investigated possible differences between vascularized and non-vascularized xenografts regarding their capacity to induce unresponsiveness. The use of pancreatic islets as primary graft neither accelerated nor decelerated the speed of rejection of the vascularized heart used as secondary graft. Furthermore, hemagglutinating and cytotoxic antibody titres responded in the same manner as in naive rats transplanted with a mouse heart. Retransplantation with pancreatic islets also resulted in complete rejection of both the primary and secondary grafts. Thus, the lack of unresponsiveness cannot simply be explained by differences, between the pancreatic and cardiac tissues, in antigen expression. In addition, intraperitoneal transplantation of mouse heart cells as primary graft resulted in rejection of a secondary cardiac graft after three days. However, it cannot be totally excluded that the time of antigen exposure had an impact on these results. In conclusion, our previous and present studies suggest that the presence of an intact vascular bed, both in the first and second graft, is necessary to create a state of unresponsiveness. Because the pancreatic islets lack an endothelial lining, they do not benefit from an unresponsiveness of the immune system. Neither are they able to induce such an unresponsiveness.     

Calcitonin gene-related peptide in Langerhans cells in psoriatic plaque lesions

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