Intestinal mononuclear cells primed by systemic interleukin-12 display long-term ability to aggravate colitis in mice.

To address whether the burst of systemic interleukin-12 (IL-12) influences intestinal inflammation elicited by luminal stimuli, we induced IL-12 release by cDNA injection in C57BL/6 mice and simultaneously started dextran sulphate sodium administration. The sequence of the inflammatory response triggered by IL-12 release was characterized by assessing myeloperoxidase activity and histological damage in colon samples on days 1, 3, 5 and 7 after colitis induction. To evaluate the persistence of IL-12 priming, colitis was induced in mice 7 or 60 days after cDNA injection. Under IL-12 influence, the development of acute colitis presented a faster and selective infiltration of inflammatory mononuclear cells in the lamina propria. Recruitment was driven by systemic cytokines rather than luminal antigens. Interestingly, when colitis was triggered 7 or 60 days after the cytokine storm, cells maintained the ability to worsen clinical signs of intestinal inflammation. Together, a systemic IL-12 burst effectively primed intestinal cells that became more prone to develop inflammatory responses. Activation was long-lasting because intestinal cells maintained their inflammatory potential and their ability to aggravate colitis.

Oxalate induces breast cancer.

BACKGROUND: Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis. METHODS: We combined Capillary Electrochromatography, histology, and gene expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast tumor. Potential carcinogenicity of oxalate was tested by its inoculation into mice. All data were subjected to statistical analysis. RESULTS: To study the biological significance of oxalates within the breast tumor microenvironment, we measured oxalate concentration in both human breast tumor tissues and adjoining non-pathological breast tissues. We found that all tested breast tumor tissues contain a higher concentration of oxalates than their counterpart non-pathological breast tissue. Moreover, it was established that oxalate induces proliferation of breast cells and stimulates the expression of a pro-tumorigenic gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated tumors when it was injected into the mammary fatpad in female mice, but not when injected into their back, indicating that oxalate does not induce cancer formation in all types of tissues. Moreover, neither human kidney-epithelial cells nor mouse fibroblast cells proliferate when are treated with oxalate. CONCLUSIONS: We found that the chronic exposure of breast epithelial cells to oxalate promotes the transformation of breast cells from normal to tumor cells, inducing the expression of a proto-oncogen as c-fos and proliferation in breast cancer cells. Furthermore, oxalate has a carcinogenic effect when injected into the mammary fatpad in mice, generating highly malignant and undifferentiated tumors with the characteristics of fibrosarcomas of the breast. As oxalates seem to promote these differences, it is expected that a significant reduction in the incidence of breast cancer tumors could be reached if it were possible to control oxalate production or its carcinogenic activity.

IL-17RA signaling reduces inflammation and mortality during Trypanosoma cruzi infection by recruiting suppressive IL-10-producing neutrophils.

Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-γ and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-γ production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-γ concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-γ production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-γ-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils.

Male rodent genital tract infection with Chlamydia muridarum: persistence in the prostate gland that triggers self-immune reactions in genetically susceptible hosts.

PURPOSE: We investigated Chlamydia trachomatis infection and its pathogenic consequences in the male rodent genital tract. MATERIALS AND METHODS: Male rats were inoculated in the meatal urethra with Chlamydia muridarum. We sought bacterial DNA at early and late times after inoculation in different parts of the male genital tract. Histological alterations and the immune response against prostate antigens were analyzed. RESULTS: Male rats showed ascending infection with wide dissemination of bacteria in the genital tract at an early time point after inoculation. At later stages bacteria persisted only in some parts of the genital tract and in the prostate gland. C. muridarum was also detected in semen in a high proportion of rats irrespective of an acute or chronic stage of infection. Histological alterations that accompanied C. muridarum were especially observed in the prostate and mainly composed of CD3+ cell infiltration. Positive humoral and cellular responses against prostate antigens were noted in a considerable number of infected rats. NOD mice, an autoimmune, prostatitis prone strain, showed a similar pattern with C. muridarum in the prostate of 100% of infected mice, which was again accompanied by mononuclear cell infiltration and antibodies against prostate antigens at early and late times after inoculation. CONCLUSIONS: Results reveal that C. muridarum infects the male rodent genitourinary tract with special persistence in the prostate gland, where it causes chronic inflammation that in turn may act as a trigger factor for self-immune reactions in susceptible hosts.

Immune-metabolic balance in stressed rats during Candida albicans infection.

We evaluated the host metabolic response to chronic varied stress during infection with the fungus Candida albicans. We used four groups of female Wistar rats: normal uninfected and unstressed, stressed, C. albicans infected and infected, and stressed. Infected rats reacted with rapid metabolic adjustments, evident as anorexia and body weight loss, partly mediated by glucocorticoids and TNF-alpha. Higher circulating levels of IL-6 and glucose (p < 0.05) revealed the progress and catabolic effect of the inflammatory response. Infected and stressed rats instead showed anorexia associated with infection and weight loss as the result of reduced food intake. This group exhibited a prompt reduction in circulating leptin on day 3 (p < 0.05), reduction in glucose levels and depletion of hepatic glycogen depots. We also evaluated the contribution of TNF-alpha, glucocorticoids, and food deprivation to liver damage. Lipid peroxidation in liver detected in the infected and infected-stressed groups was exacerbated by the glucocorticoid receptor antagonist RU 486, suggesting the modulatory activity of glucocorticoids, while hepatic fat accumulation and glycogen depletion decreased with anti-TNF-alpha treatment. Food deprivation exacerbated liver injury while the response to stress contributed to greater fungal colonization. Our findings emphasize the impact of metabolic alterations on tissue damage when the host immune activity is modulated by stress mediators.

Immune neuroendocrine interactions during a fungal infection in immunocompetent or immunosuppressed hosts.

The yeast Candida albicans belongs to the microflora of healthy individuals, although it can infect a variety of tissues ensuing changes in the host's immune status. To evaluate the effect of neuroendocrine input on the early immune response during the fungal infection, we use a 3-day paradigm of chronic varied stress in Wistar rats infected with C. albicans. We find that stress mediators contribute to the spread of the fungus and downregulate critical functions of phagocytic cells at the infection site. Phenotypic and functional alterations of effector cells account for the decreased resistance to candidiasis and condition the development of the adaptive response. Stressed hosts exhibit a higher fungal burden in kidneys and livers associated with hyphal forms. The hepatic inflammatory reaction is compromised with severe steatosis, increment of functional enzymes, marked lipid peroxidation and hepatocyte apoptosis. Moreover, infection-related sickness symptoms are significantly increased by exposure to stress with anorexia, weight loss, lack of leptin and depletion of glycogen depots. Food deprivation exacerbates the liver injury. Stress mediators perturb the complex immune and metabolic program that operates early during fungal spread and promotes severe tissue damage.

[Gastrointestinal stromal tumors: conceptual evolution]. / Tumores estromales gastrointestinales: evolucion conceptual.

Gastrointestinal stromal tumors (GISTs) constitute the largest category of primary nonepithelial neoplasms of the stomach and small bowel. They represent about 1-2% from all neoplasms of the digestive tract. They occur most commonly in the stomach and small bowel, but small series of comparable tumors have also been reported in all the other parts of the tubular gastrointestinal tract, including esophagus, colon, rectum and anus. They can also involve omentum, mesentery, uterus, retroperitoneum, mesocolon and soft tissues. Originally recognized in 1960 by Martin et. al. as a distinctive type of stromal neoplasm of the bowel, they were subsequently reported by Stout, who introduced the term leiomyoblastoma. Because of difficulties in accurately predicting the biologic behavior of these tumors, the term "smooth muscle tumor of uncertain malignant potential" (SMTUMP) has been introduced for borderline tumors. In 1983, Mazur and Clark coined the term gastrointestinal stromal tumor and suggested that these neoplasms might arise from the myenteric nervous system. Some studies have reported evidence of neuronal cell differentiation in a proportion of GISTs and the term "gastrointestinal autonomic nerve tumor (GANT) has been introduced. Kindblom et al are providing cogent arguments to suggest that GISTs show differentiation toward interstitial Cajal cells (pacemaker cells of the gastrointestinal tract). Inmunohistochemically the GISTs often reveal inmunoreactivity for vimentin. CD34 and CD 117. The aim of this paper is to perform and analysis of the historic evolution and conceptual of the GISTs.

Lack of TNFRI signaling enhances annexin A1 biological activity in intestinal inflammation.

We evaluated whether the lack of TNF-α signaling increases mucosal levels of annexin A1 (AnxA1); the hypothesis stems from previous findings showing that TNF-α neutralization in Crohn's disease patients up-regulates systemic AnxA1 expression. Biopsies from healthy volunteers and patients under anti-TNF-α therapy with remittent ulcerative colitis (UC) showed higher AnxA1 expression than those with active disease. We also evaluated dextran sulfate sodium (DSS)-acute colitis in TNF-α receptor 1 KO (TNFR1-/-) strain with impaired TNF-α signaling and C57BL/6 (WT) mice. Although both strains developed colitis, TNFR1-/- mice showed early clinical recovery, lower myeloperoxidase (MPO) activity and milder histopathological alterations. Colonic epithelium from control and DSS-treated TNFR1-/- mice showed intense AnxA1 expression and AnxA1+ CD4+ and CD8+ T cells were more frequent in TNFR1-/- animals, suggesting an extra supply of AnxA1. The pan antagonist of AnxA1 receptors exacerbated the colitis outcome in TNFR1-/- mice, supporting the pivotal role of AnxA1 in the early recovery. Our findings demonstrate that the TNF-α signaling reduction favors the expression and biological activity of AnxA1 in inflamed intestinal mucosa.

Candida albicans up-regulates the Fas-L expression in liver Natural Killer and Natural Killer T cells.

After Candida albicans arrival to the liver, the local production of proinflammatory cytokines and the expanded intrahepatic lymphocytes (IHL) can be either beneficial or detrimental to the host. Herein we explored the balance between protective inflammatory reaction and liver damage, focusing our study on the contribution of TNF-α and Fas-Fas-L pathways in the hepatocellular apoptosis associated to C. albicans infection. A robust tissue reaction and a progressive increase of IL-1ß, IL-6 and TNF-α were observed in infected animals. Blocking the biological activity of TNF-α did not modify the number of apoptotic cells observed in C. albicans infected animals. Fas-L molecule was up regulated on purified hepatic mononuclear cells and its expression progressed with the infection. In the IHL compartment, the absolute number of Fas-L+ NK and NKT cells increased on days 1 and 3 of the infection. C. albicans was also able to up regulate Fas-L expression in normal liver NK and NKT cells after in vitro contact. The innate receptor TLR2 was involved in this phenomenon. In the interplay between host factors and evasion strategies exploited by pathogens, the mechanism supported here could represent an additional way that allows this fungus to circumvent protective immune responses in the liver.

[Prostatic neuroendocrine cells]. / Células neuroendocrinas de la próstata.

From the first description of Pretl in 1944, many authors have shown different morphological and immunohistochemical studies related to prostatic neuroendocrine cells. These cells belong to a neuroendocrine system, wide disseminated network, that is found in many human tissues. They secret neuroendocrine peptides and play an important role in the glandular epithelium regulation (growing, differentiation, and exocrine secretion), in both normal and hyperplastic glands. They are also present in ordinary prostatic adenocarcinoma and in unusual small cell carcinoma. Recently, it has been suggested that prostatic neuroendocrine cells may be related to prognosis in prostatic carcinoma, particularly in cases with hormonal therapy resistant. In this study, there are 23 prostatic disorders: 11 nodular hyperplasias and 12 adenocarcinomas, and also areas of normal gland. The objective is the morphologic identification of these cells with silver impregnation technique, in normal tissue, nodular hyperplasia and adenocarcinoma. In normal gland and nodular hyperplasia, the NE cells can be seen along most of the gland or near the urethra, solitary or in small clusters. These cells are located between acinar epithelium cells and basement membrane, but they are also found within the stroma in relation to nerve endings. They characteristically contain argyrophil and argentaffin granules in the cytoplasm and exhibit cytoplasmatic processes extended to acinar or urethral lumen. Within the stroma, they are seen isolated with dendritic or ribbon-like cytoplasmatic processes. In this study, there is only one adenocarcinoma of high grade with NE cells. In this neoplasm they are increase in number, and appear isolated and more polymorphic.

Abrogation of TNFα production during cancer immunotherapy is crucial for suppressing side effects due to the systemic expression of IL-12.

For more than a decade, the cytokine interleukin-12 (IL-12) has been utilized, either alone or in combination with other drugs, as a treatment for cancer. The numerous anti-tumor properties of IL-12 still generate interest in the clinical use of this cytokine, even though it has demonstrated toxicity when administrated systemically. As an approach to overcome this toxicity, numerous laboratories have attempted to induce IL-12 expression at the site of the tumor. However for tumors that are difficult to remove surgically or for the treatment of disseminated metastases, systemic expression of this cytokine still remains as the most efficient method of administration. Nevertheless, finding alternative approaches for the use of IL-12 in the treatment of cancer and unraveling the basis of IL-12-side effects remain a challenge. In the present work we demonstrate that systemic expression of IL-12 through hydrodynamic injection of IL-12 cDNA is able to induce different types of liver lesions associated with a toxic pathology. However we report here that hepatic toxicity is diminished and survival of mice enhanced in the absence of tumor necrosis factor alpha (TNFα). This observation is in contrast to several murine models and clinical trials that postulate interferon gamma (IFNγ) as the main cytokine responsible for IL-12 toxicity. Moreover, our work demonstrates that when IL-12 cDNA is co-injected with IL-18 cDNA or when mice are pre-treated with a low dose of IL-12 cDNA prior to receiving a high dose of IL-12 cDNA, systemic levels of TNFα are almost completely abrogated, resulting in improved survival and less hepatic damage. Importantly, abrogation of TNFα signaling does not affect the strong anti-tumor activity of IL-12. Thus, neutralizing TNFα with antagonists already approved for human use offers a promising approach to abrogate IL-12 side effects during the use of this cytokine for the treatment of cancer.

BAFF mediates splenic B cell response and antibody production in experimental Chagas disease.

BACKGROUND: B cells and antibodies are involved not only in controlling the spread of blood circulating Trypanosoma cruzi, but also in the autoreactive manifestations observed in Chagas disease. Acute infection results in polyclonal B cell activation associated with hypergammaglobulinemia, delayed specific humoral immunity and high levels of non-parasite specific antibodies. Since TNF superfamily B lymphocyte Stimulator (BAFF) mediates polyclonal B cell response in vitro triggered by T. cruzi antigens, and BAFF-Tg mice show similar signs to T. cruzi infected mice, we hypothesized that BAFF can mediate polyclonal B cell response in experimental Chagas disease. METHODOLOGY/PRINCIPAL FINDINGS: BAFF is produced early and persists throughout the infection. To analyze BAFF role in experimental Chagas disease, Balb/c infected mice were injected with BR3:Fc, a soluble receptor of BAFF, to block BAFF activity. By BAFF blockade we observed that this cytokine mediates the mature B cell response and the production of non-parasite specific IgM and IgG. BAFF also influences the development of antinuclear IgG and parasite-specific IgM response, not affecting T. cruzi-specific IgG and parasitemia. Interestingly, BAFF inhibition favors the parasitism in heart. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate, for the first time, an active role for BAFF in shaping the mature B cell repertoire in a parasite infection.

High dissemination and hepatotoxicity in rats infected with Candida albicans after stress exposure: potential sensitization to liver damage.

The liver constitutes the first barrier in the control of hematogenous dissemination for Candida albicans of intestinal origin. The ability of this organ to limit the growth of the yeast and to mount an efficient inflammatory reaction is crucial in determining the outcome of the fungal infection. When rats infected with C. albicans are exposed to chronic varied stress, the cell recruitment is impaired at the site of the infection, the tissue reaction is highly disorganized in target organs and the infection evolution is more severe. At hepatic level, higher fungal burden is associated with hyphal form and the consistent presence of steatosis (fatty liver). Herein we aimed at characterizing the steatosis associated with C. albicans infection and to provide molecular evidence of the correlation among liver injury markers, stress products and the initiation of the inflammatory tissue reaction. After 3 days of stress and infection, we observed micro and macro steatosis in acinar zone 1 (specific lipid stain), higher lipid peroxidation and increased levels of serum alanine aminotransferase and gamma glutamil transferase. While infection triggered hepatic NO production and arginase activity, stress down-modulated both. Remarkably, defects in levels of TNF-alpha and NO were observed during the first step of the inflammatory response. Our results demonstrate that stress mediators down-regulate the acute inflammatory reaction in the hepatic scenario, promoting a major liver injury with particular immunopathological traits.

Neurocandidiasis, definiendo las interacciones patógeno/huésped en este particular sitio del organismo / Neurocandidiasis, defending host/pathogen intereactions in this particular site of the body

La colonización del sistema Nervioso Central por Candida Alnicans u otras especies de este género es un hecho no poco frecuente y de elevado riesgo para el huésped. La morbi-mortalidad asociada a esta presentación de la micosis y la ausencia de terapias exitosas comprometen aún más los alcances de esta patología. Otros factores que contribuyen a otorgar mayor complejidad a este escenario son las particularidades inherentes a este patógeno oportunista y las características del nicho biológico colonizado. En el presente artículo revisamos aspectos importantes del agente etiológico, sus características más destacadas y las estrategias de agresión/invasión involucradas durante su interacción con el huésped. Las peculiaridades de este sitio considerado de “Inmunoprivilegio”, los mediadores y células que contribuyen a otorgarle tal estatus y su implicancia en la evolución y severidad del proceso también son considerados. El creciente desafío de su diagnóstico, la promoción de alternativas terapéuticas y el desarrollo de nuevas estrategias constituyen un verdadero desafío que convoca a investigadores de distancias disciplinas a comprometer esfuerzos.

Tumores estromales gastrointestinales: evolución conceptual / Gastrointestinals stromal tumors: conceptual evolution

Los tumores estromales gastrointestinales (Gastrointestinal Stroma Tumors – GITs) constituyen la categoría más amplia de neoplasias no epiteliales primarias del tracto gastrointestinal y representan aproximadamente el 1-2 % de todas las neoplasias del tubo digestivo. Ocurren más frecuentemente en estomago e intestinos delgado, pero también pueden estar presentes en otros sitios del tracto gastrointestinal tubular, incluyendo esófago, colón, recto y ano. Además han sido encontrados en sitios tales como retroperineo, útero. Omento, mesocolon y tejidos blandos. Originalmente reconocidos en 1960 por Martín como una entidad clínico-patológica y un tipo distintivo de neoplasia estromal gástrica, los GITs fueron posteriormente publicados por Scout, quien introdujo el termino letomioblastoma. Debido a la dificultas en predecir con seguridad el comportamiento biológico de estos tumores, el termino “tumor de músculo liso de potencial maligno incierto” fue introducido para los tumores borderline. En 1983 Mazur y Clark acuñaron el termino “tumor estromal gastrointestinal” y sugirieron que estas lesiones podrían originarse del sistema nerviosos mientérico. Algunos estudios reportaron evidencias de una diferenciación neural en algunos GITs y fue introducido el término “tumor autonómico gastrointestinal” (GANT). En 1998 Kindblom y col. Establecieron un nuevo candidato en la línea de diferenciación de los GITs y sugirieron que estas neoplasias muestran una diferenciación inmunofenotípica hacia células intersticiales de Cajal (células marcapasos dl tracto gastrointestinal). Inmunohistoquimicamente los GITs revelan frecuentemente inmunoreactividad para vicentina (VIM) CD34 Y c-kit (CD 117). El objetivo del presente trabajo es realizar un análisis de la evolución histórica y conceptual de los GITs.

Estudio estructural comparativo de los blastomas gliales del sistema nervioso central / Comparative structural study of the glial blastomas of the central nervous system

El OBJETIVO de nuestro trabajo es comparar 2 métodos diagnósticos, y demostrar las semejanzas de las distintas Clasificaciones de los Tumores Gliales del Sistema Nervioso Central. Se realizaron técnicas de inmunomarcación para proteína gliofibrilar ácida (GFAP), e impregnaciones argénticas especiales para confrontar los hallazgos según las últimas interpretaciones histogenéticas. Estudiamos 95 Gliomas con hematoxilina-eosina y técnicas argénticas, y en 58 casos tomados al azar realizamos además la técnica para GFAP. Con ambos métodos obtuvimos resultados iguales en el diagnóstico de tumores gliales cuyas células poseen gliofibrillas: Glioepiteliomas (Ependimonas), Glioblastomas, Astroblastomas y Astrocitomas. En los Oligodendrogliomas cuyas células no poseen gliofibrillas pero sí microtúbulos, las técnicas argénticas marcaron estas células y sus prolongaciones, no así la técnica para GFAP. Hay semejanzas al comparar la Clasificación de Del Río Horttega-Polak con la de la OMS y la de otros autores, en lo referente a los Gliomas. Sólo hay diferencias en la nomenclatura de algunos tumores o en su interpretación histogenética, que no son sustanciales y están limitados, que no son sustanciles y están limitados al "Espongioblastoma Polar" y al "Gliosarcoma". Por lo tanto, creemos que la revalorización de la Clasificación de Del Río Hortega-Polak está justificada.

Células neuroendocrinas de la próstata / Prostatic neuroendocrine cells

Desde la primeira descripción del Pretl em 1944, muchos autores han realizado diferentes estudios morfológicos e inmunohistoquímicos sobre las células neuroendocrinas (NE) de la próstata. Estas células pertenecen a un sistema neuroendocrino ampliamente diseminado en muchos tejidos humanos. Las células NE prostáticas segregan distintos péptidos neuroendorinos con función reguladora sobre el epitelio glandular (crecimiento, diferenciación y secreción exocrina), tanto en la glándula normal como en la hiperplásica. También están presentes en los adenocarcinomas convencionales y en el poco frecuente carcinoma de pequeñas células. Recientemente se ha postulado que las células NE prostáticas estarían relacionadas con el pronóstico del carcinoma prostático, especialmente en aquéllos resistentes a la terapia hormonal. En este estudio hay 23 patologías prostáticas: 11 hiperplasias nodulares y 12 adenocarcinomas. El estudio comprende además áreas glandulares normales, sin lesión. El objetivo es la idenficación morfológica de éstas células con técnicas de impregnación argéntica en tejido normal, hiperplásico y carcinomatoso. En la próstata normal y en la hiperplasia modular, estas células se encuentran en toda la glándula, en forma aisladas y con prolongaciones citoplasmáticas dendríticas o acintadas. Están presentes en un solo adenocarcinoma de alto grado, en el que son más numerosas y polimorfas, y se disponen en forma aislada

Las células del sistema inmune accesorio / The cells of accessory immune system

El Sistema Retículo Endotelial (SRE), actualmente denominado Sistema Inmune Accesorio (SIA), está integrado por dos grupos celulares principales: 1- Células presentadoras de antígenos: Células Dendríticas; 2- Células procesadoras de antígenos: Macrófagos (o Histiocitos). Estas células están distribuidas por todo el organismo en órganos linfáticos, sangre, hígado, glándulas endocrinas, pulmón, piel, vasos sanguíneos, sistema nervioso central y periféricos (SNC y P), placenta, riñón y partes blandas. Las células dendríticas y los macrófagos se pueden visualizar en los tejidos con la técnica de impregnación argéntica de Del Río Hortega- Polak, y con numerosas técnicas inmunohistoquímicas específicas. Los macrófagos/monocitos se originan en la médula ósea a partir de una célula precursora común. El linaje del macrófago/monocito es: Célula precursora común que se diferencia en Unidades Formadoras de Colonias (CFU-S), luego en Unidades Formadoras de Colonias de Granulocitos/Macrófagos (CFF-G/M), posteriormente en Unidades Formadoras de Colonias de macrófagos(CFU-M), y finalmente en Monoblastos y Macrófagos/Monocitos. El origen de las células dendríticas es heterogéneo. Provienen de las mismas células precursoras mieloides que originan a los macrófagos, pero también tendrían un origen linfoide. Los macrófagos participan en diferentes funciones: 1-Fagocitosis. 2-Inmunidad natural. 3- Secreción de citocinas. 4-Presentación de antígenos. Las células dendríticas son principalmente presentadoras de antígenos y activadoras de las células T. Las proliferaciones reactivas no neoplásicas y las neoplasias malignas de las células del SIA, actualmente están siendo revisadas. Las principales entidades son entre otras: 1- Procesos Reactivos No Neoplásicos de los macrófagos: Síndomes Hemofagocíticos. Histiocitosis Sinusal con Linfadenopatía Masiva (Enfermedad de Rosai-Dorfman). Y Procesos Reactivos No Neoplásicos de las células de Langerhans: Histocitosis de células de Langerhans (Histiocitosis X). 2- Neoplasias Malignas de Células Histiocíticas: Histiocitosarcoma (antes Retículosarcoma). Histiocitosis Maligna. Microglioma del SNC. 3- Neoplasias Malignas de Células Dendríticas: Sarcoma de Células Dendríticas Foliculares y Sarcoma de Células Dendríticas Interdigitadas. Las verdaderas neoplasias malignas de células de Langerhans no han sido aún claramente demostradas. Finalmente, cabe destacar que los macrófagos y células dendríticas se encuentran...

Tumores con rabdomioblastos y neuroblastos / Tumors with rhabdomyoblasts and neuroblasts

Se evalúa uma técnica de impregnación metálica, doble impregnación de Del Río Hortega, para evidenciar rabdomioblastos y neuroblastos, con recomendaciones sobre los tiempos de impregnación para obtener mejores resultados. Las imágenes obtenidas son muy demostrativas, tanto de los elementos embrionarios del mesénquima primitivo desde mioblasto, miotubo a célula acintada rabdomiobástica con estraciones transversales, hasta los elementos neopláticos de esta estripe. Y de los neuroblastos con sus prolongaciones. El material de estudio incluye un Tumor de Wilms renal con rabdomioblastos y neuroblastos, y un Neuroblastoma de cerebelo con componente rabdomioblástico. A estas lesiones se las considera desembrioplasias. Además se estudiaron 2 Rabdomiosarcomas embrionarios botrioides, uno de ellos de presentación inusual en una mujer menopáusica, 2 Tumores müllerianos mixtos de útero y trompa de Falopio, un Rabdomioma de faringe, y 3 embriones humanos de material de aborto entre 5 y 13 semanas. Destacamos la utilidad de la doble impregnación para estudiar rabdomioblastos y neuroblastos. En los Rabdomiosarcomas se pueden ver estructuras y elementos comparables con los de la etapa embrionaria: células raquetoides, acintadas, miotubos, rabdomioblastos. El Tumor de Wilms es un tumor disembrioplásico y está constituido por el blastema renal. En él hemos encontrado rabdomioblastos y neuroblastos. En el Neuroblastoma del cerebelo servamos rabdomioblastos con cierta organicidad (ectomeséquima). Y por último describimos un caso poco frecuente de Ragdomiosarcoma botrioide de cuello uterino en una mujer menopáusica.