Evaluation of renal function and immune system cells in elderly individuals from São Paulo City

OBJECTIVES: Both renal function and immune system function decline with age. Although controversial, a significant number of studies have shown that the decline in kidney function is associated with the worsening of the immune system. These findings are reinforced by the increased susceptibility to infections and deficient immunization coverage after vaccination both in patients with chronic renal disease and in elderly individuals. Our objective was to evaluate a non-institutionalized elderly population from São Paulo City and correlate the estimated glomerular filtration rate with the percentage of lymphocytes in circulation. METHODS: A random population of 237 individuals (107 men and 130 women), ranging in age from 60 to 101 years, who were enrolled in the Health, Well-Being and Aging Study was evaluated for renal function (Modification on Diet in Renal Disease formula) and lymphocyte percentage (flow cytometry). RESULTS: Aging was associated with a decrease in the estimated glomerular filtration rate in both male and female individuals. We did not identify a significant correlation between the estimated glomerular filtration rate and either the percentage of CD4, CD8, and B cells or CD4/CD8 ratio. The median percentage of CD8+ T cells was significantly lower in individuals with an estimated glomerular filtration rate >60 mL/min/1.73 m². CONCLUSIONS: In this study, no statistical correlation was found between the estimated glomerular filtration rate and either the lymphocyte phenotype (CD4+,CD8+, and CD19+ cells) or the CD4/CD8 ratio in blood.

Ganoderma lucidum induces the expression of CD40/CD86 on peripheral blood monocytes

The major immuno-modulating effects of Ganoderma lucidum include mitogenicity and activation of immune effector cells such as T cells, macrophages and natural killer cells resulting in the production of cytokines. The purpose of this study was to evaluate the expression of CD40 and CD80 by G. lucidum-treated human peripheral blood mononuclear cells. Monocytes were isolated and incubated at 37°C and 5% CO[2] for 24 h and 48 h in the presence or absence of different concentrations of G. lucidum. Cells were then incubated with labelled monoclonal antibodies against CD14, CD40 and B7-1[CD80] molecules utilizing standard protocols, and analyzed by flow cytometry. The results showed that incubation of monocytes with G. lucidum led to marked enhancement of CD40 and B7-1 expression in a doseand time- dependent manner [p < 0.001]. G. lucidum was more effective in enhancing the expression of CD80 and CD40 molecules of cells obtained from females than male donors [p < 0.001]. G. lucidum enhanced the expression of CD40 and CD80 molecules on peripheral blood monocytic cells derived from both sexes in a dosedependent manner, with a preferential higher effect on cells obtained from female donors

Amilóide sérica A: efeitos biológicos sobre células mononucleares / Serum amyloid A: biological effects on mononuclear cells

Nos últimos anos, nosso grupo de pesquisa vem descrevendo vários efeitos da SAA em células do sistema imune no que diz respeito à expressão e liberação de citocinas pró-inflamatórias. Neste estudo centramos nossa atenção na verificação dos efeitos da SAA sobre células mononucleares. Para isto, usamos três modelos experimentais. Em murinos, descrevemos a habilidade da SAA induzir a produção de NO por macrófagos peritoneais e, com uso de animais, Knockout para TLR4, sugerimos que SAA seja um ligante endógeno do TLR4. Em células mononucleares de sangue periférico humano, a SAA induz a expressão e liberação de CCL20, uma quimiocina importante na transição da resposta imune inata para adaptativa, bem como a expressão dos fatores M-CSF e VEGF. Em células THP-1, mostramos a cinética de fosforilação de proteínas tirosina quinases promovida pela SAA e comparamos com LPS, um estímulo pró-inflamatório clássico. Ainda em células THP-1 mostramos que a SAA induz a fosforilação de duas proteínas importantes no processo inflamatório por induzirem a ativação de NFқB; a p38 e a ERK1/2. Com este estudo contribuímos com o conhecimento a respeito do papel regulatório da SAA em células mononucleares. A ação da SAA sobre estas células torna-se importante, pois estas são cruciais na resposta imune inata e também atuam como células acessórias na resposta imune adaptativa. Desta forma, evidencia-se que, no processo de fase aguda, a expressão e a síntese de SAA resultam na modulação de etapas que controlam este processo e sua progressão...

Peripheral blood cells of the armored catfish Hoplosternum littorale Hancock, 1828: a morphological and cytochemical study

Cytochemical studies are used to identify fish leukocytes and as a basis for studying the functions of these cells in cellular immune responses. In this work, we investigated the morphological features and cytochemical properties of the blood cells in the armored catfish (Hoplosternum littorale), a South American teleost. Reticulocytes, which accounted for 8-24.6% of the red blood cell population, stained with brilliant cresyl blue and contained a granular material similar to residual RNA. Thrombocytes, lymphocytes, monocytes, neutrophils, heterophils and eosinophils were identified and characterized in blood smears stained with May Grünwald-Giemsa-Wright. The lymphocytes were small, round cells with a basophilic cytoplasm and contained no periodic acid-Schiff (PAS), peroxidase or non-specific esterase activity. The thrombocytes were usually fusiform, with a hyaline cytoplasm that was acidophilic when stained with alkaline toluidine blue. The monocytes were round, with a basophilic and sometimes vacuolated cytoplasm that contained non-specific esterase activity. The neutrophils were large and round, with typical neutrophilic granules that sometimes showed moderate staining. The nuclei were rod-shaped and occasionally segmented, with PAS-positive granules that gave a weak reaction for peroxidase. The heterophils were large and round with coarse eosinophilic and basophilic, PAS-positive granules. The eosinophils were round and medium-sized, with eosinophilic granules that generally gave a negative reaction in all cytochemical stainings. The marked variation in the granulocyte morphology of H. littorale meant that a standard analysis based only on the morphology of these cells was insufficient for identifying all of the cell types.

Gap junctions in cells of the immune system: structure, regulation and possible functional roles

Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs) which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system

Galectin-1, an alternative signal for T cell death, is increased in activated macrophages

Galectin-1 belongs to an evolutionarily conserved family of animal ß-galactoside-binding proteins, which exert their functions by crosslinking the oligosaccharides of specific glycoconjugate ligands. During the past decade, attempts to identify the functional role of galectin-1 suggested participation in the regulation of the immune response. Only in the last few years has the molecular mechanism involved in these properties been clearly elucidated, revealing a critical role for galectin-1 as an alternative signal in the generation of T cell death. In the present study we will discuss the latest advances in galectin research in the context of the regulation of the immune response, not only at the central level but also at the periphery. Moreover, we will review the purification, biochemical properties and functional significance of a novel galectin-1-like protein from activated rat macrophages, whose expression is differentially regulated according to the activation state of the cells. The novel role of a carbohydrate-binding protein in the regulation of apoptosis is providing a breakthrough in galectin research and extending the interface between immunology, glycobiology and clinical medicine

Metabolic fate of glutamine in lymphocytes, macrophages and neutrophils

Eric Newsholme's laboratory was the first to show glutamine utilization by lymphocytes and macrophages. Recently, we have found that neutrophils also utilize glutamine. This amino acid has been shown to play a role in lymphocyte proliferation, cytokine production by lymphocytes and macrophages and phagocytosis and superoxide production by macrophages and neutrophils. Knowledge of the metabolic fate of glutamine in these cells is important for the understanding of the role and function of this amino acid in the maintenance of the proliferative, phagocytic and secretory capacities of these cells. Glutamine and glucose are poorly oxidized by these cells and might produce important precursors for DNA, RNA, protein and lipid synthesis. The high rate of glutamine utilization and its importance in such cells have raised the question as to the source of this glutamine, which, according to current evidence, appears to be muscle

Antígenos de diferenciación leucocitaria / Antigens of leucocyte differentiation

Los antígenos de diferenciación leucocitaria son moléculas que se detectan en la membrana de las células derivadas de la médula ósea y que se expresan con un patrón característico en cada una de las subpoblaciones de leucocitos, en sus variados estadios de diferenciación celular. En la práctica diaria, los antígenos de diferenciación leucocitaria son detectados con el empleo de anticuerpos monoclonales de origen murino; con el uso de diversas técnicas de laboratorio y estos anticuerpos, es factible el detectar, cuantificar, aislar y eliminar subpoblaciones definidas de células, tanto in vivo como in vitro. El conocimiento actual de los antígenos de diferenciación leucocitaria ha tenido un gran impacto en el campo de la reumatología, ya que ha facilitado grandemente el estudio de la fisiopatología de diversas enfermedades reumáticas, principalmente las de origen autoinmune. Además, los anticuerpos dirigidos en contra de los antígenos de diferenciación leucocitaria pueden ser de gran utilidad en el seguimiento y terapia de diversas condiciones caracterizadas por la presencia de inflamación y daño a tejidos

La interleucina 10 en enfermedades reumáticas autoinmunes / The interleukin 10 in autoimmunity rheumatic diseases

Muchas enfermedades reumáticas autoinmunes se caracterizan por hiperreactividad de sus linfocitos B que resulta en hipergammaglobulinemia y emergencia de autoanticuerpos. Recientemente se ha demostrado que la IL-10 es uno de los más potentes activadores de los linfocitos B. Induce en ellos proliferación y síntesis de inmunoglubulinas. La IL-10 también es capaz de prolongar la supervivencia de los linfocitos B al inducir en ellos la producción de bcl-2 y así protegerlos de la muerte celular programada. La IL-10 puede tener un papel importante en el desarrollo de linfomas B, particularmente en el contexto de una replicación anormal del virus de Epstein-Barr. En artritis reumatoide, síndrome de Sjögren y lupus eritematoso existe una alteración de la regulación genética de la IL-10. Esta alteración se observa en linfocitos B y monocitos. El resultado de esa anormalidad conduce a la estimulación de los linfocitos B por vía autócrina y parácrina. En este artículo revisamos los mecanismos de la regulación genética de la IL-10 y su papel en enfermedades reumáticas autoinmunes. Proponemos, además, nuevas modalidades terapéuticas que pudieran modular los efectos de la IL-10 en estas enfermedades

Humoral and cellular immune response within the subarachnoid space of patients with neurocysticercosis

To study the immune response within the subarachnoid space in patients with neurocysticercosis, we measured the cerebrospinal fluid contents of immunoglobulins A, E, G, and M in 38 patients and the contents of the proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients. The same measurements were made in 30 neurological patients without inflammatory or immune-mediated disorders. Each immunoglobulin and cytokine, including the gender and age of the patient, was compared by multiple regression analysis with the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct correlation was found of IgM with cell content (p<0.058) and with ELISA values (p<0.027); of age with protein content (p<0.006); of IL-6 with protein content (p<0.018) and of IL-1b with ELISA values (p<0.004). An inverse correlation was found of glucose with ELISA values (p<0.008). A complex function of the immune response within the subarachonid space was observed: mean values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values of IgA, TNF-alpha and IFN-gamma were similar to those of controls

Efectos in vitro de echinococcus granulosus en las células del hospedador / In vitro effects of echinococcus granulosus on host cells

The realtionship between the parasite, echinococcus granulosus and the host, is reviewed in terms of its effect on non immune and immune cells. An explanation of a concomitant inmunity in hydatid infection is given, where existing substances would not only help to inmunize the host against the parasite, but they would also allow the hydatid cyst to survive against the host immune system. This situation would be defined as an immuno-homeostatic relationship. Its understanding would be important for the control of hydatid disease

Linfocitos Th1, Th2 y enfermedad / Lymphocytes Th1, Th2 and disease

Al activarse, los linfocitos T CD4+ muestran una producción de citocinas que usualmente sigue tres patrones distintos y estereotipados; estos patrones son producidos por subpoblaciones discretas que se denominan Th1, Th2 y Th0. Las células Th1 secretan principalmente interferón- (IFN-), interleucina-2 (IL-2) y factor de necrosis tumoral (FNT), citocinas que tienen un papel clave en la respuesta inmune mediada por células y el fenómeno de hipersensibilidad de tipo tardío. Las células Th2 producen IL-4, IL-5, IL-6, IL-9, IL-10 e IL-13, las cuales juegan un papel clave en la generación de la respuesta inmune humoral. Existe una regulación negativa recíproca entre las células Th1 y Th2 ya que ciertas citocinas de las primeras (principalmente IFN-) y de las segundas (IL-4, IL-10) tienen un efecto inhibitorio sobre células Th2 y Th1 respectivamente. Las células Th0 producen citocinas tipo Th1 y Th2. Es posible determinar el patrón de citocinas que están siendo producidas en un tejido, lo que permite inferir si ocurre una activación preferencial de células Th1, Th2 o Th0 en ese sitio. La activación preferencial de subpoblaciones de linfocitos CD4+ tiene un papel importante en la patogenia de enfermedades infecciosas y autoinmunes. Los pacientes con lepra lepromatosa tienen una activación preferencial de células Th2, lo cual conduce a una enfermedad diseminada con ausencia de respuesta inmune celular. La activación preferencial de células Th2 puede ser de importancia en la patogenia de enfermedades autoinmunes generalizadas, en tanto que las células Th1 tienen importancia en padecimientos autoinmunes órgano-específicos. Resulta factible el manipular in vivo la activación preferencial de linfocitos Th1 y Th2, lo cual puede tener implicaciones terapéuticas importantes