Physiologic roles of P2 receptors in leukocytes.

Since their discovery in the 1970s, purinergic receptors have been shown to play key roles in a wide variety of biologic systems and cell types. In the immune system, purinergic receptors participate in innate immunity and in the modulation of the adaptive immune response. In particular, P2 receptors, which respond to extracellular nucleotides, are widely expressed on leukocytes, causing the release of cytokines and chemokines and the formation of inflammatory mediators, and inducing phagocytosis, degranulation, and cell death. The activity of these receptors is regulated by ectonucleotidases-expressed in these same cell types-which regulate the availability of nucleotides in the extracellular environment. In this article, we review the characteristics of the main purinergic receptor subtypes present in the immune system, focusing on the P2 family. In addition, we describe the physiologic roles of the P2 receptors already identified in leukocytes and how they can positively or negatively modulate the development of infectious diseases, inflammation, and pain.

Mapa de evidências sobre a efetividade clínica da moxabustão: informe executivo / Evidence map on the clinical effectiveness of moxibustion: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos da moxabustão. A partir de uma ampla busca bibliográfica foram incluídos no mapa 64 estudos de revisão. Todos os estudos foram avaliados, caracterizados e categorizados por um grupo de pesquisadores da área de acupuntura e Medicina Tradicional Chinesa. Principais Achados: ● Os estudos primários incluídos nas revisões estão concentrados principalmente em países como China (51 estudos), Coreia do Sul (10 estudos) e Itália (4 estudos). ● As revisões sistemáticas avaliaram efetividade, eficácia, segurança e custo-efetividade e incluíram ensaios clínicos randomizados (RCTs) (62), RCTs + ensaios controlados não randomizados (1) e ensaios clínicos + estudos observacionais (1). ● Para avaliar o nível de confiabilidade das 64 revisões, se aplicou a ferramenta AMSTAR2 resultando em 4 revisões de nível alto, 2 revisões de nível moderado, 21 revisões de nível baixo e 37 revisões de nível criticamente baixo. ● A maioria das evidências disponíveis concentra-se no grupo das Doenças crônicas não transmissíveis e aplicada para os desfechos osteoartrite, hipertensão arterial e hérnia de disco. ● Os desfechos mais observados foram osteoartrite (7 revisões), hipertensão arterial (5 revisões), trabalho de parto (5 revisões). Implicações para a prática e pesquisa: ● Os efeitos positivos (26 revisões) foram relacionados principalmente a osteoartrite (4 revisões), trabalho de parto (4), hérnia de disco (2) e dispepsia (2); ● Os efeitos potencialmente positivos (23 revisões) foram identificados em osteoartrite (3 revisões), hipertensão arterial (2), constipação (2), transtorno gastrointestinal (2) entre outros; ● Identificou-se feitos inconclusivos/misturados em 14 revisões. Para estes efeitos serem mais bem avaliados, uma ampliação do número de estudos se faz necessária; ● Apenas uma revisão (hipertensão arterial) referiu ausência de efeito; ● Efeitos negativos não foram observados.

The map provides an overview of the evidence on the effects of moxibustion. Based on a broad bibliographic search (PubMed, BVS, EMBASE and CINAHL) 64 review studies were included in the map (51 systematic reviews with meta-analysis, 6 systematic reviews of randomized controlled studies, 3 systematic reviews and 4 meta-analyses). All studies were evaluated, characterized, and categorized by a group of researchers in the field of acupuncture and Traditional Chinese Medicine. Main Findings: ● Primary studies included in the reviews are mainly concentrated in countries such as China (51 studies), South Korea (10 studies) and Italy (4 studies). ● Systematic reviews evaluated effectiveness, efficacy, safety and cost-effectiveness and included randomized clinical trials (RCTs) (62), RCTs + non-randomized controlled trials (1) and clinical trials + observational studies (1).● To assess the reliability level of the 64 revisions, the AMSTAR 2 tool was applied resulting in 4 high-level reviews, 2 moderate-level reviews, 21 low-level reviews, and 37 critically low-level reviews.● Most of the available evidence is related to osteoarthritis, hypertension, and intervertebral disc displacement outcomes.● The most frequently observed outcomes were osteoarthritis (7 reviews), hypertension (5 reviews) and obstetric labor (5 reviews). Implications for practice and research: ● Positive effects (26 reviews) were mainly related to osteoarthritis (4 revisions), obstetric labor (4), intervertebral disc displacement (2) and dyspepsia (2). ● Potentially positive effects (23 reviews) were identified in osteoarthritis (3 revisions), hypertension (2), constipation (2), gastrointestinal disorders (2) among others. ● Inconclusive effects were identified in 14 reviews. For these effects to be better evaluated, an increase in the number of studies is necessary. ● Only one revision (hypertension) reported no effect. ● Negative effects were not observed.

El mapa proporciona una visión general de la evidencia sobre los efectos de la moxibustión. A partir de una amplia búsqueda bibliográfica (PubMed, BVS, EMBASE y CINAHL) se incluyeron 64 estudios de revisión en el mapa (51 revisiones sistemáticas con metaanálisis, 6 revisiones sistemáticas de estudios controlados aleatorios, 3 revisiones sistemáticas y 4 metaanálisis). Todos los estudios fueron evaluados, caracterizados y categorizados por un grupo de investigadores en el campo de la acupuntura y la Medicina Tradicional China. Principales hallazgos:● Los estudios primarios incluidos en las revisiones se concentran principalmente en países como China (51 estudios), Corea del Sur (10 estudios) e Italia (4 estudios); ● Las revisiones sistemáticas evaluaron la efectividad, la eficacia, la seguridad y la relación costo-efectividad e incluyeron ensayos clínicos aleatorios (RCTs) (62), RCTs + ensayos controlados no aleatorios (1) y ensayos clínicos + estudios observacionales (1); ● Para evaluar el nivel de confiabilidad de las 64 revisiones, se aplicó la herramienta AMSTAR 2 que resultó en 4 revisiones de alto nivel, 2 revisiones de nivel moderado, 21 revisiones de bajo nivel y 37 revisiones de nivel críticamente bajo; ● La mayor parte de la evidencia disponible está relacionada con los resultados de la osteoartritis, la hipertensión y la hernia discal; ● Los resultados observados con mayor frecuencia fueron osteoartritis (7 revisiones), hipertensión (5 revisiones) y trabajo de parto (5 revisiones). Implicaciones para la práctica y la investigación: ● Los efectos positivos (26 revisiones) se relacionaron principalmente con la osteoartritis (4 revisiones), el trabajo de parto (4), la hernia discal (2) y la dispepsia (2); ● Los efectos potencialmente positivos (23 revisiones) se identificaron en osteoartritis (3 revisiones), hipertensión (2), estreñimiento (2), trastornos gastrointestinales (2), entre otros; ● Se identificaron efectos no concluyentes en 14 revisiones. Para que estos efectos sean mejor evaluados, es necesario un aumento en el número de estudios; ● Sólo una revisión (hipertensión) no informó ningún efecto; ● No se observaron efectos negativos.

Modulation of intercellular communication in macrophages: possible interactions between GAP junctions and P2 receptors.

Gap junctions are connexin-formed channels that play an important role in intercellular communication in most cell types. In the immune system, specifically in macrophages, the expression of connexins and the establishment of functional gap junctions are still controversial issues. Macrophages express P2X(7) receptors that, once activated by the binding of extracellular ATP, lead to the opening of transmembrane pores permeable to molecules of up to 900 Da. There is evidence suggesting an interplay between gap junctions and P2 receptors in different cell systems. Thus, we used ATP-sensitive and -insensitive J774.G8 macrophage cell lines to investigate this interplay. To study junctional communication in J774-macrophage-like cells, we assessed cell-to-cell communication by microinjecting Lucifer Yellow. Confluent cultures of ATP-sensitive J774 cells (ATP-s cells) are coupled, whereas ATP-insensitive J774 cells (ATP-i cells), derived by overexposing J774 cells to extracellular ATP until they do not display the phenomenon of ATP-induced permeabilization, are essentially uncoupled. Western-blot and reverse-transcription polymerase chain reaction assays revealed that ATP-s and ATP-i cells express connexin43 (Cx43), whereas only ATP-s cells express the P2X(7) receptor. Accordingly, ATP-i cells did not display any detectable ATP-induced current under whole-cell patch-clamp recordings. Using immunofluorescence microscopy, Cx43 reactivity was found at the cell surface and in regions of cell-cell contact of ATP-s cells, whereas, in ATP-i cells, Cx43 immunoreactivity was only present in cytosolic compartments. Using confocal microscopy, it is shown here that, in ATP-s cells as well as in peritoneal macrophages, Cx43 and P2X(7) receptors are co-localized to the membrane of ATP-s cells and peritoneal macrophages.