RESUMEN
E-cadherin, a member of the cadherin family of transmembrane adhesion receptors, is critical for cutaneous barrier function, as it promotes keratinocyte and Langerhans cell adhesion in the epidermis. Recent murine models of chronic inflammation identified new E-cadherin expressing subsets of mononuclear phagocytes, including alternatively activated macrophages and selected inflammatory dendritic cells. It has been shown in vitro that expression of E-cadherin by murine macrophages promotes their homotypic aggregation and fusion to multinucleated giant cells (MNGCs), a signature cell type of granulomatous inflammation. The purpose of this study was to assess E-cadherin expression on histiocytes and giant cells in cutaneous granulomas in humans. E-cadherin expression was evaluated by immunohistochemistry of formalin-fixed paraffin-embedded skin biopsies of foreign body granulomas (n = 21) and sarcoidosis (n = 21). The results showed consistent membranous E-cadherin staining pattern on mononucleated histiocytes and MNGCs in both granuloma types. These E-cadherin expressing histiocytes are distinct from dermal Langerhans cells because they lacked CD1a expression. Our findings suggest that E-cadherin expressing mononuclear histiocytes are likely precursors for MNGCs in cutaneous granulomas and may play a critical role in disease pathogenesis.
Asunto(s)
Cadherinas/análisis , Células Gigantes/química , Granuloma de Cuerpo Extraño/metabolismo , Histiocitos/química , Sarcoidosis/metabolismo , Enfermedades de la Piel/metabolismo , Piel/química , Antígenos CD , Antígenos CD1/análisis , Biomarcadores/análisis , Biopsia , Células Gigantes/patología , Granuloma de Cuerpo Extraño/patología , Histiocitos/patología , Humanos , Inmunohistoquímica , Sarcoidosis/patología , Piel/patología , Enfermedades de la Piel/patologíaRESUMEN
OBJECTIVE: The objective of this study is to determine the prevalence of the contralateral ear changes in human temporal bones of donors with chronic otitis media. STUDY DESIGN: Transversal. MATERIAL AND METHODS: The temporal bones were examined under light microscopy and then described. Chronic otitis media was defined by the presence of irreversible inflammatory alterations in the middle ear cleft. The contralateral ear was defined as the normal or the less affected ear. To compare the qualitative variables, the chi test was used. Spearman's nonparametric test was used for correlations. P values less than or equal to .05 were considered significant. RESULTS: We studied 85 pairs of temporal bones. Cholesteatoma was observed in 22.4% of the more damaged ears. The prevalence of contralateral ears with alterations was 91.8%. The main alterations were granulation tissue (81%), effusion (58%), and tympanic membrane retractions (35%). There was a direct and moderately strong correlation between the extent of granulation tissue in the more damaged ear and the contralateral ear (r(s) = 0.345, P = .004). A strong correlation was observed between the extent of cholesteatoma in the more damaged ear and in the contralateral ear (rs = 0.617, P < .001). CONCLUSION: We observed a high prevalence of changes in the contralateral ear. There was a direct correlation between the extent of both granulation tissue and cholesteatoma between the two ears, demonstrating that the more extensive the manifestation of these pathologies in the more damaged ear, the greater they will be in the contralateral ear.
Asunto(s)
Colesteatoma del Oído Medio/patología , Otitis Media/patología , Otosclerosis/patología , Adulto , Colesteatoma del Oído Medio/epidemiología , Colesterol/metabolismo , Enfermedad Crónica , Estudios Transversales , Femenino , Granuloma , Granuloma de Cuerpo Extraño/epidemiología , Granuloma de Cuerpo Extraño/metabolismo , Granuloma de Cuerpo Extraño/patología , Humanos , Masculino , Otitis Media/epidemiología , Otosclerosis/epidemiología , Prevalencia , Índice de Severidad de la Enfermedad , Membrana Timpánica/patologíaRESUMEN
Epithelioid cells (ECs) found in granulomas are thought to derive from mononuclear phagocytes. Although GM-CSF and/or IL-4 are known to promote cell differentiation their role in the development of ECs has never been demonstrated. Here we showed that mouse macrophages treated exclusively with recombinant IL-4 (rIL-4) differentiate into epithelioid-like cells. Macrophages cultivated with rIL-4 presented a fried-egg shape, and ultrastructural studies revealed membrane interdigitations, cytoplasmic vesicles, prominent Golgi complex, and rough endoplasmic reticulum. Compared with controls, rIL-4 treated cells displayed increased expression of MHC class II molecules and of Migration Inhibitory Factor-Related Protein-14. Whereas mannose receptor-mediated phagocytosis was increased, Fcgamma-receptor mediated phagocytosis and the production of nitric oxide were decreased in treated cultures. All these features overlap those reported for ECs from granulomatous lesions. In conclusion, treatment of mouse peritoneal macrophages with rIL-4 drives their in vitro differentiation to an epithelioid phenotype and provides a tool to investigate the biology of ECs.
Asunto(s)
Células Epitelioides/inmunología , Granuloma de Cuerpo Extraño/inmunología , Inmunofenotipificación , Interleucina-4/farmacología , Macrófagos/inmunología , Animales , Células Cultivadas , Células Epitelioides/metabolismo , Células Epitelioides/patología , Células Epitelioides/ultraestructura , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Granuloma de Cuerpo Extraño/metabolismo , Granuloma de Cuerpo Extraño/patología , Macrófagos/metabolismo , Macrófagos/patología , Macrófagos/ultraestructura , Masculino , Ratones , Ratones Endogámicos BALB C , Fagocitosis/inmunología , Proteínas Recombinantes/farmacologíaRESUMEN
The microbicidal activity of macrophages in an inflammatory milieu has been related to the production of a large number of cytokins and intermediary metabolites of oxygen and nitrogen among them, nitric oxide (NO). Considering that granulomatous inflammation is predominantly composed of macrophages and epithelioid cells, we decided to investigate the participation of NO in this peculiar type of inflammation. Two models were used: glass cover slip implantation into the subcutaneous tissue of mice and, the inoculation of live bacillus Calmette-Guérin (BCG) into the footpad of the animals. Using a histochemical method for the detection of NO synthase and of the concentration of citrulin metabolized by cells obtained from cover slips implanted on different time intervals or BCG-activated peritoneal cells, it was possible to demonstrate that epithelioid cells do not produce NO. Cells from granuloma induced by BCG inoculation express NO synthase, with different degrees of reactivity with a higher intensity in the cytoplasm of cells located in the edge of the lesions. The expression of NO synthase in the cytoplasm of these cells decreases with the age of the lesions. It could also be demonstrated that in mice treated with l-name, an inhibitor of NO metabolism, the lesions induced by BCG lost the granulomatous architecture, were necrotic, and had a significant increase in the bacillary load of the lesion. These data allow us to conclude that NO production by macrophages is a determining factor in the organization of the granulomatous lesion and that it also controls the bacterial load in BCG-induced lesions in mice.
Asunto(s)
Granuloma de Cuerpo Extraño/metabolismo , Macrófagos Peritoneales/enzimología , Mycobacterium bovis , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Tuberculoma/metabolismo , Análisis de Varianza , Animales , Arginina/metabolismo , Citrulina/metabolismo , Células Epitelioides/metabolismo , Granuloma de Cuerpo Extraño/patología , Masculino , Ratones , Tuberculoma/microbiología , Tuberculoma/patologíaRESUMEN
Twenty eight albino Wistar rats were implanted with two 100 mg lead spheres: 14 received the implant in the peritoneum (P) and 14 in the thigh (T). Variations in the activity of delta-aminolevulinic dehydratase (ALAD), of urinary delta-aminolevulinic acid (ALAU), of hematoporphyrins (HP) and of lead blood levels (BPb) were then determined at 30, 60 and 90 days with respect to basal values. Parallel determinations were performed by the same schedule in 7 rats implanted with two glass beads and in 8 sham animals receiving surgical incision alone. Techniques employed for ALAD were Berlin and Schaller; for ALAU, Tomokuni and Ogata; for HP, Piomelli; and for BPb, atomic absorption spectrophotometry. As indicators of lead presence, HP and ALAU proved better, both in P and in T rats. The replacement of lead buckshot for small game hunting by other less toxic elements is recommended.