Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.

Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 × 10-3Μ completely inhibited platelet aggregation (p<0.05), decreased TXB2 levels (p<0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p<0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 ± 34, 450 ± 34 and 62 ± 2.4% (p<0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.

Tumor necrosis factor-alpha and the cytokine network in psoriasis / Fator de necrose tumoral-alfa e a rede de citocinas na psoriase

New molecular methods of research have greatly expanded the knowledge about the role of cytokines in several diseases, including psoriasis. The work orchestrated by these peptides is essential for the communication between resident inflammatory cells (keratinocytes and endothelial cells) and infiltrating cells (neutrophils, lymphocytes, Langerhans cells). This is a complex network due to redundancy, synergism and, sometimes, the antagonism of cytokines, which prevents full understanding of the pathogenesis of the disease. Currently, it seems premature to try to establish a main actor, but TNFalpha participates in all stages of psoriatic plaque development, as we shall see.

A introdução de novos métodos moleculares de investigação ampliou muito o conhecimento sobre o papel das citocinas em diversas doenças, entre elas a psoríase. O trabalho orquestrado desses polipeptídeos é fundamental na comunicação entre as células inflamatórias residentes (queratinócitos e células endoteliais) e infiltrantes (neutrófilos, linfócitos, células de Langerhans). Trata-se de uma rede complexa devido à redundância, ao sinergismo e, por vezes, ao antagonismo das citocinas, o que dificulta a compreensão da fisiopatogenia da doença a partir de um mecanismo linear. No momento atual, parece precoce tentar estabelecer um regente, mas o TNF-alfa se destaca em todos os passos do desenvolvimento da placa psoriásica, como veremos a seguir.

Contribution of dendritic cell/T cell interactions to triggering and maintaining autoimmunity

Under healthy conditions, there is a balance between tolerance to self-tissue constituents and immunity against foreign antigens. Autoimmunity diseases (AD) take place when that equilibrium is disrupted and the immune response is directed to self-antigens, leading to injury or destruction of host tissues. The mechanisms conducing to the loss of immune tolerance remain largely unknown. The recent appearance of biological therapies has contributed to significant reduction in morbidity. However, currently available therapies are associated with important side effects and work only as palliative treatments. Dendritic cells (DCs) have emerged as key players in developing and maintaining adaptive immunity due to their capacity to prime and modulate T cell function. Therefore, because DCs work as central modulators of immune tolerance, it is likely that alterations in their function can lead to the onset of autoimmune-inflammatory diseases. By modulating DC function, novel pathways in antigen-specific tolerance could be established. In this article, the possible contribution of altered DC-T cell interactions to the onset of autoimmunity are discussed. In addition, we expand on the notion that some of the functions of these cells could be relevant targets for intervening therapies aimed to restore the balance or even prevent the loss of tolerance.

Mycobacterium tuberculosis and dendritic cells: recognition, activation and functional implications.

The highly complex nature of interactions of Mycobacterium tuberculosis with cells of the immune system has puzzled researchers the world-over in understanding the pathogenesis and immunology associated with tuberculosis (TB). This has contributed to the delay in development of effective vaccine(s) for TB. Several excellent studies have provided only a glimpse of the kind and degree of immune responses elicited following infection by mycobacteria. Preferred entry via respiratory route results in the capture of mycobacteria by alveolar macrophages that eventually become their long-term hosts. Since the pathogen is rarely cleared this has resulted in the human population serving as a large reservoir for mycobacteria. Owing to their unique ability to prime naïve and memory T cells, dendritic cells (DCs) play important and indispensable roles in the initiation and maintenance of protective immune responses following infection. The kind of immune response initiated by DCs with respect to mycobacteria determines the character of immune responses mounted by the host against the pathogen. The profile of cytokines and chemokines secreted as a result of infection of DCs by mycobacteria further plays an important role in defining the course of infection. This minireview attempts to highlight key interactions of mycobacteria with dendritic cells. We discus the uptake of mycobacteria by DCs followed by DC activation and the spectrum of immune responses initiated by infected/activated DCs, followed by numerous ways the pathogen has devised to subvert protective responses.

Aplicación de una cámara de flujo para el análisis de la aglutinación eritrocitaria mediada por anticuerpos monoclonales / Application of the flow chamber technique to the analysis of the erythrocyte agglutination mediated by monoclonal antibodies

El conocimiento de la energía involucrada en las interacciones célula-célula tiene importantes implicaciones en las ciencias biológicas y médicas. Los glóbulos rojos se adhieren entre si cuando macromoléculas específicas o no específicas (aglutininas) enlazan células adyacentes de manera irreversible o reversible. La técnica de la cámara de flujo fue utilizada para evaluar la afinidad de un anticuerpo monoclonal analizando la disociación de un doblete (dos células aglutinadas por el anticuerpo) determinando la energía de adhesión. Esta técnica permite aplicar una tensión de corte uniforme paralela a la interfase de adhesión de un aglutinado de dos células fijado sobre la superficie inferior de un microcanal. La tensión produce el desprendimiento progresivo de la célula superior del doblete. La observación microscópica de la separación producida en el aglutinado aislado y la obtención de imágenes secuenciales con una cámara CCD (Charged Coupled Device), permite determinar la relación entre la tensión de corte aplicada (sigma) y el porcentaje de separación de las células del doblete. A partir de estos resultados calculamos la energía de disociación por unidad de área membranal adherida(gamma d), valor igual a 8.92 x 10 elevado a -19 N.cm por moléculas de anticuerpo. Del análisis de los resultados, se concluye que la tensión de corte necesaria para disociar el doblete es proporcional a la densidad superficial de moléculas de anticuerpo y a la densidad antigénica de los eritrocitos.