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Effects of asbestos on epithelioid cell lines.

The in vitro effects of asbestos fibers on the growth and viability of CHO cells, an epithelioid cell line derived from Chinese hamster ovary, and on K-22 cells, an epithelial cell line derived from rat liver, have been studied. Relatively low concentrations of asbestos (10 micrograms/ml) were quite cytotoxic to both cell types. A sample of chrysotile asbestos was more toxic than samples of crocidolite or amosite. The toxic factor could not be extracted from the asbestos and toxicity occurred only if there was physical contact between the fibers and the cells. Although the phorbol ester class of tumor promoters induces the synthesis of plasminogen activator in various cell cultures, asbestos did not induce this protease in epithelioid or fibroblast cell cultures. The results obtained are compared to previous in vitro results obtained with fibroblast or macrophage cultures and are discussed in terms of their possible relevance to asbestos-induced fibrosis and tumorigenesis.

Animals

Ultrastructural features of epithelioid cell granuloma induced by intradermal injection of xenogeneic nerve tissue.

Epithelioid cell granulomas were induced in rabbits previously sensitised with human sensory peripheral nerve extract by skin testing with homogenate of sural nerve. Ultrastructurally some of the cells contained in their cytoplasm abundant and dilated rough endoplasmic reticulum filled with a moderately dense product while the cytoplasm of other cells contained numerous membrane-bound vesicles. These cells show all the ultrastructural characteristics of epithelioid cells found in human granulomatous disease and in human states of granulomatous hypersensitivity. Thus we have developed an animal model which supports the concept of granulomatous hypersensitivity as a distinct entity in humans to be differentiated from foreign body and delayed-type hypersensitivity reactions. The model may also prove important in elucidating the pathogenesis of granuloma formation in non-lepromatous leprosy and other granulomatous disease and in defining the nature of the products of epithelioid cells.

Animals

Epithelioid cell cultures from rat small intestine. Characterization by morphologic and immunologic criteria.

Rat small intestinal epithelial cell lines have been established in vitro and subcultured serially for periods up to 6 mo. These cells have an epithelioid morphology, grow as monolayers of closely opposed polygonal cells, and during the logarithmic phase of growth have a population doubling time of 19--22 h. Ultrastructural studies revealed the presence of microvilli, tight junctions, an extensive Golgi complex, and the presence of extracellular amorphous material similar in appearance to isolated basement membrane. These cells exhibit a number of features characteristic of normal cells in culture; namely, a normal rat diploid karyotype, strong density inhibition of growth, lack of growth in soft agar, and a low plating efficiency when seeded at low density. They did not produce tumors when injected in syngeneic animals. Immunochemical studies were performed to determine their origin using antisera prepared against rat small intestinal crypt cell plasma membrane, brush border membrane of villus cells and isolated sucrase-isomaltase complex. Antigenic determinants specific for small intestinal epithelial (crypt and villus) cells were demonstrated on the surface of the epithelioid cells, but they lacked immunological determinants specific for differentiated villus cells. An antiserum specifically staining extracellular material surrounding the cells cultured in vitro demonstrated cross-reactivity to basement membrane in rat intestinal frozen sections. It is concluded that the cultured epithelioid cells have features of undifferentiated small intestinal crypt cells.

Animals

Facsimile epithelioid cells obtained from stimulated peritoneal macrophages and their secretory activity in vitro.

Mouse peritoneal macrophages collected after exposure to new born calf serum in vivo were found to have some of the morphological and ultrastructural features attributed to epithelioid cells. These features were accentuated by short term culture in vivo or in vitro. Three accepted varieties of epithelioid cell were reproduced, i.e., those with predominant rough ER, those with predominant smooth vesicles and the plasmacytoid variety. Cells resembling fibroblasts were not seen, nor were lymphoid cells. The facsimile epithelioid cells had considerable secretory activity for a range of macrophage enzymes. They retained the phagocytic capacity and the surface receptors of macrophages but to a reduced extent. It is suggested that epithelioid cells are a form of stimulated macrophage, especially effective in enzyme secretion and liable to appear after excitation of the cell membrane by pinocytosis rather than phagocytosis.

Animals

The differentiation of monocytes into macrophages, epithelioid cells, and multinucleated giant cells in subcutaneous granulomas. I. Fine structure.

The morphological changes occurring in monocytes during their differentiation into macrophages, epithelioid cells, Langhans-type giant cells, and foreign-body-type giant cells were investigated in foreign-body granulomas induced by subcutaneous implantation of pieces of Melinex plastic. Analysis based on Adams's (1974) criteria for discrimination between the several types of cell of the monocyte line, showed that each type has a characteristic type of granule. Primary and secondary granules, numerous in the Golgi area of monocytes were generally found close to the cell membrane and decreased in number in maturing macrophages. This was accompanied by an increase in the number of microtubules. Mature macrophages show numerous characteristic macrophage granules, which are round (average diameter: 280 nm) and have a halo between the limiting membrane and granular matrix. Mature epithelioid cells have characteristic epithelioid cell granules, and multinucleated giant cells a heterogenous population of granules. Fusing macrophages generally have their Golgi areas facing each other, and also show a reduced thickness of the cell coat. The morphology of the multinucleated giant cell is closely related to the number of nuclei present. In Langhans-type giant cells, which generally have two to ten nuclei, a giant centrosphere with numerous aggregated centrioles is found. In transition forms between Langhans-type and foreign-body-type giant cells, which generally contain 10--30 nuclei, the centrioles show less aggregation. In the foreign-body-type giant cells, which generally have more than 30 nuclei, centrioles are virtually absent and never aggregated. These differences between the Langhans-type giant cells, the foreign-body-type giant cells, and the transition forms, support our previous finding that Langhans-type giant cells are the precursors of foreign-body-type giant cells.

Animals

The differentiation of monocytes into macrophages, epithelioid cells, and multinucleated giant cells in subcutaneous granulomas. II. Peroxidatic activity.

The peroxidatic (PO) activity of monocytes differentiating into macrophages, epithelioid cells, and multinucleated giant cells in subcutaneous granulomas was investigated with three different media for the demonstration of PO activity. Irrespective of the stage of differentiation, these cells did not show PO activity in the rough endoplasmic reticulum (RER) or nuclear envelope. In addition, it was found that the morphologically characteristic types of granule of the various cells of the monocyte line (the primary granules and secondary granules of monocytes, the macrophage granules, and the epithelioid cell granules), all have distinct cytochemical characteristics. Monocytes lose their primary and secondary granules during differentiation into mature macrophages. Simultaneously, the granules of both types become elongated and the secondary granule lose their halo. In contrast to monocytes, mature macrophages may contain a few microperoxisomes. During the differentiation of macrophages into epithelioid cells or multinucleated giant cells there is an increase in the number of microperoxisomes.

Animals

Melanoma resembling spindle and epithelioid cell nevus.

Three cases of malignant melanoma resembling spindle and epithelioid cell nevus histologically are presented. Lesions having histologic features of spindle and epithelioid cell nevus (Spitz nevus or juvenile melanoma) at or after puberty should be regarded with caution, particularly when they are heavily melanized. Such lesions are in a histologic "gray zone" and may be malignant.

Adolescent

Immunological and non-immunological phagocytosis by inflammatory macrophages, epithelioid cells and macrophage polykaryons from foreign body granulomata.

Inflammatory macrophages, epithelioid cells and macrophage polykaryons were obtained on the surface of round glass coverslips inserted into the subcutaneous tissue of mice and removed at different intervals. About 90 per cent of the macrophages and polykaryons express IgG, C and non-specific surface receptors, involved in phagocytosis, up to 15 days after coverslip implantation. In 21-day-old lesions, about 50 per cent of these cells lose the IgG resed with IgM and complement but do not incorporate these particles and are poorly phagocytic for glutaraldehyde-treated horse red blood cells. The ultrastructural study of these cells demonstrates that they are macrophages which have undergone epithelioid transformation. Whole-body irradiation of mice bearing implanted coverslips of 7 days duration reveals that 6 days after irradiation, the great majority of macrophages and multinucleate cells have acquired epithelioid characteristics. It is suggested that the loss of immunological receptors during epithelioid transformation in granulomas may protect bacteria and be disadvantageous to the host.

Age Factors

Epithelioid cell granulomata in the mucosa of the small intestine in Whipple's disease.

This report is the first description of sarcoid-like epithelioid cell granulomata in the mucosa of the small intestine in a case of Whipple's disease. The epithelioid cells do not contain PAS-positive material or products of bacterial degradation. Their ultrastructural features characterize them as histiocytes which have become secretory rather than phagocytic. These sarcoid-like lesions are considered to be a morphological manifestation of an immunological process in Whipple's disease and not to represent evidence of sarcoidosis as a concomitant or associated disorder.

Granuloma

Ultrastructural observations on epithelioid cell granulomas induced by zirconium in the guinea-pig.

An ultrastructural study has been made of the allergic-type nodular granulomas that can be induced in guinea-pigs sensitised to sodium zirconium lactate. Lesions taken at the peak of granuloma development 7 days after skin testing contained epithelioid cells which could be recognised particularly by their content of rough endoplasmic reticulum, fimbriated cell membrane and typical nuclear appearance. Multinucleate giant cells were also seen. These cells were characterised by their large number of lysosome-like dense bodies and phagocytic structures. Both epithelioid cells and multinucleate giant cells were similar to those described in zirconium granulomas in man. However, these cells differed in a number of respects from similar cells observed in human sarcoidosis. A constant feature of the guinea-pig lesions was the presence of large numbers of apparently active fibroblasts.

Animals

[Epithelioid cell. Ultrastructural data during various pathological conditions].

A morphological study permitted us to show that the epithelioid cell is an active cell, the characteristic vesicles of which seem to be linked to the presence of a glycoprotein substance which passes through the Golgi apparatus and becomes accumlated in the lysosomes owing to their richness in acid phosphatase. A fraction of this substance may be secreted into the extra-cellular medium, without it being possible to determine its precise nature and whether this function is carried out only by this cell.

Connective Tissue

[Hodgkin's disease with epithelioid cells. Study of 56 cases having undergone an exploratory laparotomy].

Histological examination of the various specimens taken during an exploratory laparotomy for Hodgkin's disease revealed the presence of epithelioid cells in 56 cases out of a total of 235 patients (i.e. 23.8 p. 100). These cells were disseminated throughout the lymphoid tissue or grouped in clumps, in plaques or, more rarely, as true follicles. They were found either in contact with Hodgkin's lesions or at a distance in organs free of disease. They were found in Lukes-Rye histological types 1, 2 and, above all, 3. Their significance remains unknown. The most likely hypotheses would appear to be those of a response to the accumulation of substances to be eliminated (tumour antigens?) or those of a disorder in cellular immunity.

Adolescent

Nevus of large spindle and/or epithelioid cells (Spitz's nevus).

By now it is well recognized that there is a benign melanocytic nevus, common in the young and common enough in adults, that has histological features that are confusable with those of malignant melanoma. The anomaly is usually referred to as benign juvenile melanoma, sometimes as Spitz's nevus, and, by some histopathologists, as spindle and epithelioid cell nevus. All the histological subtleties and variations of the condition are still not fully appreciated and some of them are still being misinterpreted as those of malignant melanoma. We herewith present a study designed to clarify the issue and offer firm criteria for histological differentiation of the nevus in point from malignant melanoma. We also suggest a new name for it and supporting arguments therefor.

Adolescent

Benign epithelioid cell nevi of the iris.

Two benign acquired melanocytic lesions of the iris stroma had distinctive clinical and pathologic features. One tumor was loculated and polypoid, suggesting ectopic glandular tissue, while the other was a flat tumor with a rich surface capillarity. Both lesions histologically were composed of mononucleated, binucleated, and multinucleated hypopigmented epithelioid and elongated "myoid" cells, widely separated in a finely fibrillar eosinophilic stroma. The ultrastructural features of one case included hyperconvoluted nuclei, conspicuous cytoplasmic filaments are rare, filamentary-striated (leptomeric) structures, scant organelles and inclusions except for numerous mitochondria and glycogen granules, small and infrequent melanosomes, and a fibrillary extracellular matrix focally organized into banded basement membrane material.

Adult

Properties of human epithelioid cells established in vitro by a herpesvirus [IBRV(HMC)] isolated from cytomegalovirus-transformed human cells.

Infectious bovine rhinotracheitis virus [IBRV(HMC)], a double-enveloped herpesvirus, was isolated from human embryo lung fibroblasts transformed by cytomegalovirus (CMV). This agent was identified as an IBRV strain that was antigenically related to human CMV. Inoculation of a primary human kidney cancer cell culture with IBRV(HMC) resulted in persistent infection and subsequent establishment of a cell line [IBRV(HMC)HKC-1]. Virus-related nuclear, cytoplasmic, and cell membrane antigens were detected in these cells in early in vitro passages by anticomplement and indirect immunofluorescence tests. Infectious virus was rescued from one of the cell sublines after temperature-shock treatment at passage 26. Karyotypic analysis confirmed the human origin of the cells. Control uninfected kidney cancer cells survived only six in vitro passages. The established cells grew to more than 100 in vitro passages 1 year after initiation of the experiments and induced an epithelioid cancer of variable morphology that infiltrated nerves and muscles when inoculated sc into athymic nude mice.

Adenocarcinoma

Florid epithelioid cell and sarcoid-type reaction associated with non-Hodgkin's lymphoma.

Five patients suffering from non-Hodgkin's lymphoma associated with an intense infiltration of epithelioid histiocytes and even sarcoid-type granulomas in the involved tissue are described. A similar tissue reaction, at both involved and uninvolved sites, has been described in patients with Hodgkin's disease. The cause of this reaction may be immunological; its prognostic significance still awaits elucidation. In the case of non-Hodgkin's lymphomas, it may cause difficulty in diagnosis of lymphoma and hence may result in unnecessary delay in the initiation of therapy.

Adult