Renal interstitial foam cells are macrophages

Immunohistochemical studies on renal biopsies from eight patients with various types of glomerulonephritis showed that the interstitial foam cells belonged to the monocyte-macrophage lineage. There was a strong association between hypercholesterolaemia and the presence of renal interstitial foam cells.     

脂肪分化相关蛋白在巨噬细胞和泡沫细胞中的表达

目的:观察脂肪分化相关蛋白(ADRP)在单核细胞向巨噬细胞和泡沫细胞分化过程中的表达变化.方法:体外诱导THP-1单核细胞分化为巨噬细胞和泡沫细胞,应用Real time RT-PCR和Western blot测定ADRP在基因水平和蛋白水平的表达.结果:单核细胞分化为巨噬细胞时ADRP的表达水平无明显变化,当进一步分化为泡沫细胞时,ADRP的mRNA和蛋白表达水平均显著增加.结论:单核细胞向巨噬细胞分化时对ADRP的表达无影响,而由巨噬细胞进一步向泡沫细胞分化时ADRP的表达升高.     

Familial hydrocephalus with normal cognition and distinctive radiological features

Hydrocephalus is a clinically and genetically heterogeneous condition. Individuals with posterior fossa abnormalities have an increased risk of developing hydrocephalus. The Dandy-Walker malformation, Dandy-Walker variant, and mega-cisterna magna (MCM) seem to represent a continuum of developmental anomalies of the posterior fossa. Here we describe the natural clinical history and the radiological features of a family with autosomal or X-linked dominant inheritance of MCM and hydrocephalus of variable severity. The affected family members demonstrate similar structural brain abnormalities including midline cyst, colpocephaly, MCM with a large posterior fossa and minimal vermian hypoplasia. The cognitive development of the affected individuals is normal. L1CAM and FOXC1 gene involvement in the pathogenesis of the disease in this family was excluded. The rare possibility of autosomal dominant or X-linked dominant inheritance and variable penetrance and expressivity must always be considered in genetic counseling of families with hereditary hydrocephalus.     

Coexistence of two lymphomas with distinctive histologic, ultrastructural, and immunologic features.

The unusual coexistence of two distinct lymphomas in 44-year-old woman is described. Nodular, poorly differentiated lymphocytic lymphoma and diffuse histiocytic lymphoma were present in separate sites and were readily distinguished both histologically and ultrastructurally. In addition, the lymphocytic lymphoma was shown to be derived from complement receptor B lymphocytes of follicular center cell type, whereas the histiocytic lymphoma cells were devoid of complement receptors, receptors for IgG (Fc receptors), and surface immunoglobulin. Despite intensive chemotherapy and radiation therapy, the patient died within eight months of the initial diagnosis. Although histiocytic lymphoma was widely disseminated at autopsy, lymphocytic lymphoma was not found. Presumably the histiocytic lymphoma was refractory to therapy, in contrast to the lymphocytic lymphoma, which was selectively eradicated.     

Ultrastructural localization of tissue factor on monocyte-derived macrophages and macrophage foam cells associated with atherosclerotic lesions

The expression of tissue factor (TF) antigen by circulating monocytes, cultured macrophages, and macrophages associated with atherosclerotic lesions was ultrastructurally analysed using immunogold labeling. A subpopulation of macrophages associated with the intimal surface overlying lesions had a significant TF expression. Macrophages and macrophage foam cells that projected from the intima into the arterial lumen also expressed a high level of TF (14-fold increase over control). In contrast, circulating monocytes and macrophages in culture did not express TF above background control levels. This TF expression by macrophages in vivo but not by macrophages cultured from either normal or hypercholesterolemic animals suggests that monocyte activation and macrophage transition, as measured by TF expression, is lesion-dependent and not stimulated solely by intimal attachment, surface migration, or hypercholesterolemia. These results further suggest that macrophages and foam cells associated with early lesions of atherosclerosis can initiate fibrin formation, which could contribute to lesion complications and transition to a fibromuscular stage.     

Structural and histochemical features of cortical thymic epithelial cells in mice with chemically-induced lymphoid leukemia

Ultrastructural, enzyme histochemical (acide phosphatase, adenosine triphosphatase, neutral 5'-nucleotidase) and immunohistochemical (cytokeratins with monoclonal antibodies BH11 and BC3) features of the thymus cortical epithelial cells of leukemic DBA/2 inbred mice have been studied. In the leukemic mice epithelial cells appeared possessing some ultrastructural and histochemical features of cell activation. Lympho-epithelial complexes, composed mainly of BH11 and BC3 immunoreactive cells and of lymphoid cells were subcapsulary and subseptally found. It is discussed on the eventual involvement of the lympho-epithelial complexes in the intrathymic leukemogenesis during lymphoid leukemia.     

Biochemical and histochemical features of human cultured cells (EUE) adapted to hypertonic medium.

EUE cells from a human heteroploid line cultured in hypertonic medium (0.274 M NaCl) modify their lipid pattern: sulfolipid concentration reaches 86 to 90 microgram/mg protein whilst it ranges between 19 to 32 microgram/mg in cells cultured in isotonic medium. Ganglioside concentration reaches 2.6 nmoles of sialic acid/mg protein (after 75 days) and 13 (after 85 days) in hypertonic saline medium. Whilst it is 0.5 in isotonic medium. Phospholipid concentration does not show any similar change. Cytoenzymatic analysis reveals that dehydrogenases (lactate, G-6-P dehydrogenases, tetrahydrofolate reductase and NADH diaphorase) appear strongly enhanced in cells grown on hypertonic medium. On the contrary higher acid phosphatase and ATPase activity was demonstrable in cells grown on isotonic medium. These results are similar (except for ATPase activity) to those observed in salt secreting glands involved in strong osmotic work. The results are discussed in relation to the problem of energy supply in cells performing osmotic work.     

Syncytial giant-cell hepatitis. Sporadic hepatitis with distinctive pathological features, a severe clinical course, and paramyxoviral features

BACKGROUND AND METHODS. We describe a new form of hepatitis, occurring in 10 patients over a period of six years, characterized clinically by manifestations of severe hepatitis, histologically by large syncytial giant hepatocytes, and ultrastructurally by intracytoplasmic structures consistent with paramyxoviral nucleocapsids. RESULTS. The patients ranged in age from 5 months to 41 years. The tentative clinical diagnosis before biopsy was non-A, non-B hepatitis in five patients and autoimmune chronic active hepatitis in the others. Five patients underwent liver transplantation; the others died. The diagnosis of syncytial giant-cell hepatitis was established pathologically. The liver cords were replaced in all 10 patients by syncytial giant cells with up to 30 nuclei. In 8 of the 10 the cytoplasm contained pleomorphic particles of 150 to 250 microns, filamentous strands, and particles of 14 to 17 nm with peripherally disposed spikes resembling paramyxoviral nucleocapsids. Structures resembling degenerated forms were found in the other two patients. One of two chimpanzees injected with a liver homogenate from the index patient had an increase in the titer of paramyxoviral antibodies, probably an anamnestic reaction to previous paramyxoviral infection, suggesting that a paramyxoviral antigen but not viable virus was present in the liver homogenate. CONCLUSIONS. Although further virologic studies will be required for precise classification, we believe that paramyxoviruses should be considered in patients with severe sporadic hepatitis.     

Arterial macrophages and regenerating endothelial cells express P-selectin in atherosclerosis-prone apolipoprotein E-deficient mice

P-selectin expression has been reported in platelets, endothelial cells, and vascular smooth muscle cells in response to vascular injury. Here, we report P-selectin expression on macrophages in the arterial wall after carotid denudation injury and spontaneous atherosclerosis in atherosclerosis-prone apoE-deficient (apoE(-/-)) mice. Double-immunofluorescence staining revealed robust P-selectin expression in macrophage-rich regions of both denudation-induced carotid neointimal lesions and innominate atherosclerotic plaques. Co-localization of P-selectin with macrophages was verified at the single cell level using double immunostaining plus 4,6-diamidino-2-phenylindole (for nuclei) counterstaining. No platelet staining was seen in association with the macrophage staining, excluding platelet contamination. Furthermore, P-selectin mRNA expression was readily detectable in macrophage-rich plaques of atherosclerotic innominate arteries and blood monocyte-derived macrophages from apoE(-/-) mice. Strong P-selectin expression was also seen in the areas of regenerated endothelium after arterial injury. In addition, co-localization of P-selectin with vascular smooth muscle cells was readily observed in denudation-injured carotid arteries at 7 and 14 days. We conclude that macrophages in carotid injury-induced neointimal lesions and spontaneous atherosclerotic plaques of the innominate artery acquire the ability to express P-selectin, as does regenerating endothelium. These findings provide a potential new paradigm in macrophage-mediated vascular inflammation, atherosclerosis, and neointimal hyperplasia after arterial injury.     

Identification of foam cells in human atherosclerotic lesions as macrophages using monoclonal antibodies

Four monoclonal antibodies against human monocyte/macrophage epitopes were used in an immunoperoxidase procedure to identify foam cells in atherosclerotic plaques from human aortas and coronary arteries. All antibodies gave positive reactions with the majority of foam cells observed in fatty streaks and advanced atheromas. Immunoperoxidase staining correlated with oil red O and nonspecific esterase-positive areas. Use of the immunohistochemical technique on Bouin's-fixed, paraffin-embedded tissue gave good results that afforded better localization and cell morphology than observed with frozen sections. In addition to the identification of the majority of foam cells as monocytic in origin, the technique described allowed visualization of membrane-bound extracellular droplets that were monocyte derived within necrotic cores of atheromas, indicating a contribution by dead macrophages to the lipid of atherosclerotic plaques.     

''Organoid'' thymoma: a well-differentiated variant with distinctive clinicopathological features

The present paper describes the clinical, histological and immunohistochemical features of five cases of 'organoid' thymoma. The histological hallmark of this lesion is the prominent and diffuse 'organoid' pattern, defined by the presence of several areas of medullary differentiation. These areas, which are strictly reminiscent of the medullary area of the normal thymus, are scattered within a neoplastic tissue resembling the thymus cortex, the overall appearance mimicking that of normal thymus. All cases shared common clinical features; they were non-invasive or minimally invasive tumours arising in young or middle-aged female patients. Although the incidence of 'organoid' thymoma is low (5.2% in our series), our morphological, immunohistochemical and clinical data suggest that this peculiar tumour may represent a well-differentiated variant of thymoma, with low-grade aggressiveness and a distinct clinicopathological profile.     

Sequential histochemical staining for resident and recruited macrophages

A new histochemical technique is described that permits differentiation of resident from recruited macrophages by staining of paraffin sections of tissues from rats and mice. Resident macrophages are identified by their ability to phagocytose and retain intravenously injected colloidal Prussian blue. New macrophages that emigrate into tissue are identified by phagocytosis of a second colloid, iron dextran. Paraffin sections of formalin-fixed tissues are sequentially stained for the presence of the two colloids with different chromogens, the endogenous pseudo-peroxidase activity of colloidal Prussian blue used to catalyze the polymerization of diaminobenzidine and after conversion of iron dextran to Prussian blue, the second colloid used to catalyze the polymerization of tetramethylbenzidine. The staining results in resident macrophages staining brown while newly recruited macrophages stain blue. The studies have shown that colloidal Prussian blue is stable in vivo and neither loses its catalytic activity nor undergoes extensive redistribution. They also show that the technique can be used to measure Kupffer cell recruitment stimulated by complete Freund's adjuvant in rats and tumor-associated macrophage recruitment in subcutaneous and spontaneous liver metastases in mice.     

PPARs配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的影响

目的：观察PPAR α、γ配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达的影响。方法：体外诱导THP-1单核细胞转化为巨噬细胞、泡沫细胞，分别加入PPAR α配体氯贝特（clofibrate）、PPARγ配体吡格列酮(pioglitazone)共同培养，应用Real-time RT-PCR和Western blotting测定巨噬细胞、泡沫细胞中EMMPRIN基因和蛋白表达，ELISA测定细胞培养上清液MMP-9浓度，Zymgraphy法测定MMP-9活性。结果：氯贝特和吡格列酮均能显著抑制巨噬细胞和泡沫细胞EMMPRIN的表达，此抑制作用与PPAR α、γ配体抑制MMP-9分泌及活性的趋势一致。结论：PPAR α、γ配体均可抑制巨噬细胞、泡沫细胞EMMPRIN的表达，下调EMMPRIN可能是PPARs配体抑制粥样斑块局部MMPs产生的机制之一。     

Enzyme histochemical comparison of biomphalaria glabrata amebocytes with human granuloma macrophages

In fresh water snails, amebocytes are the principal cells that react to parasitic infection. Ultrastructurally, amebocytes resemble mammalian macrophages. To clarify the relationship between amebocytes and macrophages, we compared the histochemical staining for seven enzymes in Biomphalaria glabrata snail amebocytes, both in the amebocyte-producing organ (APO) and in the encapsulation reaction formed around parasite sporocysts with the staining in macrophages from the lymph nodes of patients with sarcoid or tuberculosis. Snails were infected with Echinostoma paraensei and Schistosoma mansoni miracidia. APOs and ventricular tissue with encapsulated parasites were fixed and embedded in glycol methacrylate monomer. Hardened blocks were sectioned at 2 micron and stained for alkaline phosphatase, acid phosphatase, alpha-naphthyl acetate esterase (ANAE), ATPase, peroxidase, 5'nucleotidase, and chloroacetate esterase. The amebocyte-producing organ contained cells that were positive for acid phosphatase, ANAE, and ATPase. Amebocytes in the capsules formed around echinostome sporocysts showed stronger staining for the same three enzymes. Capsules did not form around schistosome sporocysts, but the connective tissue around them contained numerous amebocytes that were also positive for these three enzymes. The amebocyte enzyme histochemistry resembled that in human granuloma macrophages, but differed from that in neutrophils. The increased expression of enzymes in amebocytes involved in the encapsulation reaction as compared to those in the APO was reminiscent of the alterations observed when human monocytes convert to tissue macrophages. These studies support the hypothesis that the amebocyte is an "invertebrate macrophage."     

阻断MaxiK 通道对人单核细胞源性巨噬细胞向泡沫细胞分化的抑制作用

目的研究高电导钙离子激活钾通道(MaxiK通道)在人单核细胞源性巨噬细胞向泡沫细胞分化的过程中,其mRNA和蛋白的表达及作用。方法采用密度梯度离心加贴壁黏附法,从男性健康志愿者的外周血中分离单核细胞,经5d培养后分化为巨噬细胞。在建立人巨噬细胞源性泡沫细胞模型的基础上,采用免疫细胞化学染色法、RT-PCR及蛋白印迹,研究MaxiK通道α-亚单位的表达,并观察其特异性阻断剂-Paxilline对摄取氧化型低密度脂蛋白(OxLDL)的巨噬细胞中胆固醇代谢的影响。结果将巨噬细胞同30mg/LOxLDL于37℃孵育60h后,细胞体积增大,并有许多红色的脂质颗粒沉积于细胞质内,细胞内的总胆固醇(TC)、游离胆固醇(FC)及胆固醇酯(CE)的含量均显著增加,CE/TC从(14.437±6.781)%提高到(57.946±3.507)%(n=7,P<0.05);而MaxiK通道α-亚单位mRNA及蛋白的表达水平没有明显改变(P>0.05)。5和10μmol/L的Paxilline能显著减少巨噬细胞内TC、FC及CE的含量,CE/TC分别降至(41.217±5.584)%和(18.017±11.559)%(n=7,P<0.05),细胞内沉积的红色脂质颗粒也明显减少。结论阻断MaxiK通道能抑制人单核细胞源性巨噬细胞向泡沫细胞分化。     

Characterization of macrophages in the decidual atherotic spiral artery with special reference to the cytology of foam cells

Acute atherosis is characteristic in the spiral arteries of the placental bed of preeclampsia and a wide range of pregnancy disorders. The arterial lesion is histologically characterized by fibrinoid necrosis of the vessel walls with infiltration of foam cells, which under a light microscope appears similar to that seen in atherosclerosis. Although acute atherosis is currently considered as atheromatous-like lesions, the precise cellular mechanisms inducing these changes remain unelucidated. By histochemistry, immunohistochemistry, and electron microscopy, we investigated the decidual spiral arteries obtained by placental bed biopsy from 11 preeclamptic and 15 nonpreeclamptic women. In the decidual spiral arteries of preeclamptic patients, acute atherosis was observed in 23.5% (20/85 arteries). Fibrin deposition and accumulation of foam cells were observed more frequently in preeclamptic patients than in nonpreeclamptic patients. Endothelial cells remained in the atheromatous lesion, while the smooth muscle layer surrounding fibrin and foam cells became thin and was finally destroyed. The foam cells were immunohistochemically shown to be macrophages and neutral fat and phospholipids were histochemically demonstrated in them. Ultrastructurally, their cytoplasm was occupied by variously sized lipid droplets and membrane-bound myelin-like granules (myelinosomes). Plasma concentration of monocyte chemoattractant protein 1 (MCP-1), a potent monocyte chemoattractant factor, was significantly elevated in preeclamptic patients compared with normal healthy controls (P 0.01). In conclusion, injuries to the smooth muscle layer and intramural fibrinoid necrosis may result in infiltration of monocytes into the arterial walls, their maturation into macrophages, and the transformation into foam cells. Considering that atherosclerosis is developed by accumulation of lipid-laden macrophages and migration and proliferation of smooth muscle cells, the roles of macrophages in acute atherosis differ from those in atherosclerosis.     

Significance of PAM histochemical reaction in delineating macrophages

Periodic acid methenamine silver staining has been used for proof of the existence of carbohydrates in both paraffin and resin embedded tissues. The staining was applied to delineate macrophages that have been well known as cells of mononuclear phagocyte system by stainable nature for lysosomes, and it is found to be useful method for detection of macrophage. Fetal macrophage, which is often observed in placental villi, is called the highly vacuolated cell. Vacuoles in the cytoplasm seem to be empty with light microscopic staining, but it is clarified that they contain a full amount of carbohydrate. The present result leads us to the necessity of reconsidering the functional aspect of fetal macrophage.     

The distinctive specificity of antigen-specific suppressor T cells.

Although suppressor T cells have been cloned in only a few instances, the existence of a functional cadre of T cells that acts to downregulate the immune response is well documented. In this review Eli Sercarz and Urszula Krzych describe studies on suppressor T-cell (TS-cell) specificity that provide some support for the conclusion that the TS cell is a distinctive cell type with an expressed repertoire that is different from that expressed by helper T (TH) cells. They go on to explore the interaction between cells recognizing TS-cell-inducing determinants (SDs) and TH-cell-inducing determinants (HDs), and their relationship to immunogenicity and Ir gene effects.