Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.     

Circulating E-Selectin Levels in Chronic Hepatitis C Patients with Normal or Elevated Transaminase Before and After Alpha-Interferon Treatment

E-selectin, an adhesion molecule of the selectin family, is involved in leukocyte adhesion to the endothelium and in the cellular immunological reactions. Expression of this molecule, in fact, is physiologically absent, but it becomes evident on sinusoidal lining cells during inflammatory liver disease. The aim of this study was to evaluate the behavior of E-selectin in chronic hepatitis C (CH-C) patients with persistently normal transaminase in comparison to patients with CH-C and elevated transaminase, and its changes during alpha-interferon therapy. Immunohistochemical localization of E-selectin was also performed on liver tissue specimens of both groups. Fifty-eight subjects were divided into 3 groups: group A included 18 patients with CH-C and persistently normal transaminase; group B 20 patients with CH-C and persistently elevated transaminase levels and group C included 20 healthy subjects, representing the control group. The first two groups were treated with r-IFN at a dose of 6 MU 3 times a week for 3 months and followed-up with 3 MU 3 times a week for another 3 months. Serum baseline values of E-selectin in groups A and B were significantly higher than those in group C (P < 0.04), but there was no difference between groups A and B. Furthermore, there was a trend toward higher E-selectin values as histological severity increased (r = 0.69; P < 0.0001). Post-treatment E-selectin serum values showed a moderate decrease in both groups, but only among responder patients; while E-selectin levels were unchanged in non responders. Immunohistochemical localization showed no staining for E-selectin in normal liver specimens, while there was a quite similar staining for E-selectin in the two groups of patients. In conclusion, this study shows that serum E-selectin levels in patients with CH-C and persistently normal transaminase are higher than in controls and they are associated with severity of liver disease. Liver of these patients express E-selectin molecules, suggesting an activation of the immune system almost identical to that of patients with CH-C and elevated transaminase. In both groups only responder patients showed a moderate decrease below baseline serum values.     

Activation of Human Monocytes for Enhanced Production of Interleukin 8 During Transendothelial Migration in Vitro

Interleukin-8 (IL-8) is a chemokine for polymorphonuclear leukocytes (PMNs) and lymphocytes, which promotes the extravasation of these inflammatory cells. In this study, we investigated IL-8 synthesis induced by the adhesive interaction between monocytes and endothelial cells during transmigration and the capacity of transmigrated monocytes to produce IL-8. Cocultured human monocytes and human umbilical vein endothelial cell (HUVEC) monolayers induced the synefgistic production of IL-8, compared with cultures of either monocytes or HUVEC monolayers alone. Coculture-induced IL-8 production almost doubled after HUVECs were stimulated with IL-1. The induced IL-8 mRNA expression was consistent with the protein data, indicating the de novo synthesis of IL-8 by the coculture. Monoclonal antibodies (mAbs) against IL-8 inhibited the transendothelial chemotactic activity of the supernatants for PMNs by 55%. Immunohistochemistry revealed that both adherent and transmigrated monocytes and unstimulated HUVECs expressed IL-8 protein, whereas nonadherent monocytes did little. Transmigrated monocytes spontaneously secreted a 3.8-fold greater amount of IL-8 than the initial monocytes. Coculture-induced IL-8 production was inhibited about 30% by polyclonal Abs against IL-, IL-1, or tumor necrosis factor , while it was not affected by mAbs against intercellular adhesion molecule 1 or vascular cell adhesion molecule 1. The results suggested that adhesive interaction during the transmigration of monocytes through HUVEC monolayers activates both cell types to produce IL-8 and that transmigrated monocytes are capable of producing ample IL-8.     

M-CSF和IL-10对人单核细胞表面分子表达的影响

本文采用流式细胞术检测人外周血单核细胞表面CD14、CD2 3、CD6 4、CD11b、CD18、CD2 9表达 ,研究巨噬细胞集落刺激因子 (M CSF )和白细胞介素 (IL ) 10对单核细胞炎症效应和免疫效应功能的影响。结果显示 ,(1)M CSF诱导单核细胞表面CD14及CD2 3分子的表达 (P <0 0 5 )。IL 10抑制CD2 3的表达 ,促进CD6 4的表达 ,并协同M CSF诱导单核细胞CD14的表达 ,拮抗M CSF对CD2 3的诱导作用。M CSF能协同IL 10对单核细胞CD6 4的诱导作用 ;(2 )M CSF能诱导单核细胞表面CD11b及CD18的表达 (P <0 0 5 )。结论 :M CSF通过促进单核细胞表面CD11b、CD18、CD14、CD2 3的表达及协同促进CD6 4的表达而促进单核细胞粘附、炎性渗出、IgG及IgE依赖的细胞杀伤和吞噬功能 ,促进单核 巨噬细胞在炎症反应、体液免疫应答效应阶段发挥效应细胞功能。IL 10通过促进CD6 4的表达 ,增强体液免疫应答效应阶段单核 巨噬细胞的免疫效应功能 ,但通过抑制CD2 3的表达 ,下调IgE介导的体液免疫效应。     

Placental site trophoblastic tumor of the mediastinum

Choriocarcinoma has been described as the most frequent subtype of mediastinal germ cell tumors showing trophoblastic differentiation. We report a unique case of a placental site trophoblastic tumor, which developed in the mediastinum of a 14-year-old boy 2 years after the resection of a mature teratoma. The recurrent tumor was composed of a grossly hemorrhagic and necrotic mass. Histologically, diffusely infiltrating large polygonal cells with focal nodular growth and a teratomatous part containing mature intestinal, respiratory, and squamous epithelium with adjacent cutaneous adnexal structures were found. The typical morphologic features included vessel wall infiltration by the neoplastic cells with fibrinoid deposits and geographic necroses within the tumor masses. Characteristic diffuse positivity for melanoma cell adhesion molecule and human leucocyte antigen G was found on immunohistochemical investigation, confirming the diagnosis of placental site trophoblastic tumor. The patient died 1 year later after polychemotherapy. The outcome of this rare tumor is similar to the reported poor clinical outcome in patients with mediastinal choriocarcinomas.     

Does infection with Chlamydia pneumoniae and/or Helicobacter pylori increase the expression of endothelial cell adhesion molecules in humans?

Objective   To investigate if Chlamydia pneumoniae and/or Helicobacter pylori seropositivity is associated with elevated levels of soluble endothelial cell adhesion molecules (sCAMs) as markers of atherosclerotic activity.
Methods   Immunoglobulin A (IgA) and IgG antibodies to the two bacteria, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin were measured in coronary heart disease (CHD) patients ( n  = 193) and age- and sex-matched controls ( n  = 193). Two different serological methods were used for the detection of Chlamydia antibodies: Labsystems microimmunofluorescence to detect species-specific C. pneumoniae antibodies and Medac's recombinant enzyme-linked immunosorbent assay to detect genus-specific lipopolysaccharide antibodies.
Results   The concentrations of sICAM-1 and E-selectin were higher in CHD patients with positive vs. negative Chlamydia lipopolysaccharide IgA ( P  = 0.044 for both). H. pylori antibodies alone did not predict raised levels of sCAMs, but in CHD patients sICAM-1 was increased with IgA seropositivity to both bacteria compared to double seronegativity ( P  = 0.034). Concentrations of sVCAM-1 were elevated in CHD patients with double IgA seropositivity compared to those with Chlamydia lipopolysaccharide IgA seropositivity alone ( P  = 0.018).
Conclusion   Our results may indicate that C. pneumoniae contributes to increased inflammation in CHD, and that this contribution is even more pronounced when present in combination with H. pylori IgA antibodies.     

冠状动脉粥样硬化性心脏病细胞间黏附分子1基因 K469E多态性的研究

目的探讨细胞间黏附分子1(intercellularadhesionmolecule1,ICAM1)基因K469E多态性及其血浆水平与中国汉族冠状动脉粥样硬化性心脏病(简称冠心病)之间的关系。方法利用巢式PCR和免疫酶联吸附测定技术对160例冠心病患者和164名非冠心病对照进行ICAM1基因K469E多态性及其血浆水平的检测和对比分析。结果冠心病组K等位基因频率、ICAM1血浆水平均高于非冠心病对照组(P<0·05);含K等位基因的个体ICAM1血浆水平(344.34±128.59μg/L)高于不含K等位基因的个体(303·54±108·74μg/L),差异有统计学意义(P=0.008);且其患冠心病(心肌梗塞)的危险性升高(P=0.006,OR=2·158,95%CI:1.250~3.727);K等位基因与吸烟在影响冠心病发生危险性方面有协同作用。结论在中国汉族人群中存在ICAM1基因K469E多态性,其中K等位基因有可能是冠心病的遗传危险因素。     

Chronic morphine treatment increases the expression of the neural cell adhesion molecule in the dorsal horn of the mouse spinal cord

It is well known that prolonged exposure to morphine results in tolerance to morphine-induced antinociception. In the present study, we found that mice that were tolerant to morphine-induced antinociception exhibited an increase in immunoreactivity for the neural cell adhesion molecule in the dorsal horn of the spinal cord, which was highly overlapped with immunoreactivity for the increased metabotropic glutamate receptor 5 induced by morphine. These findings support the idea that repeated stimulation of μ-opioid receptors increases the expression of neural cell adhesion molecule and metabotropic glutamate receptor 5. This phenomenon leads to the enhanced excitatory synaptic transmission in the dorsal horn of the spinal cord, and in turn suppresses the morphine-induced antinociception.     

Fibre type specific expression of Leu19-antigen and N-CAM in skeletal muscle in various stages after experimental denervation

Leu-19 antigen, which seems to be identical with neural cell adhesion molecule (N-CAM), plays a major role in the innervation of muscle cells, and in adult muscle appears after denervation and during regeneration of muscle fibres, where it acts as part of a signalling system increasing the probability of re-innervation. This combined enzyme-histochemical and immunohistochemical study examined whether this signalling process was regulated in a uniform or differential pattern for type 1 and type 2 muscle fibres. The subscapular nerve of 18 rabbits was transsected with subsequent complete denervation of the supraspinatus muscle. Leu19 and N-CAM immunohistochemistry was performed 2 to 64 days after surgery. Whereas in normal muscle there are virtually no Leu-19/N-CAM positive muscle fibres; from day 2 after denervation an increasing proportion of fibres expressed Leu-19/N-CAM, prior to any neurogenic atrophy. In the early stage of denervation Leul9/N-CAM expression was confined to type 1 fibres. After 11 days nearly all fibres were Leul9/N-CAM positive irrespective of their fibre type. Sixty-four days after denervation type 1 fibres became Leu19/N-CAM negative, while atrophic type 2 fibres showed intensive staining. Thus, expression of Leu-19 antigenity is differently regulated in both fibre types.     

Malignant peripheral nerve sheath tumor of small round cell type with pleomorphic spindle cell sarcomatous areas

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation.