RESUMEN
Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.
Asunto(s)
Apoptosis/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Animales , Antagonistas de Estrógenos/farmacología , Caballos , Macrófagos/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Tamoxifeno/farmacologíaRESUMEN
Reaginic antibodies (IgE and some IgG subclasses) and mast cells play important roles in the induction of type I immediate hypersensitivity reactions. These antibodies bind through their Fc fragment to high affinity receptors (FcεRI) present in the membrane of mast cells and basophils. The cross-linking of the receptor initiates a coordinated sequence of biochemical and morphological events that results in exocytosis of secretory granules containing pre-formed inflammatory mediators, secretion of newly formed lipid mediators, and secretion of cytokines. Previously, several studies have investigated the role of reaginic antibodies in the pathogenesis of Recurrent Airway Obstruction (RAO). However, whereas the immunological aspects of RAO have been extensively studied, the precise sequence of events involved in the pathogenesis remains not completely understood, and the role of IgE in this disease remains controversial. Therefore, in this study, several bioassays were conducted to determine whether reaginic antibodies from RAO-affected horses have the ability to activate mast cells. These bioassays involved measuring degranulation of rat peritoneal mast cells, activation of NF-κB and morphological changes in basophilic leukemia cells (RBL-2H3) following incubation with horse serum from RAO-affected horses that were sensitive and insensitive to Aspergillus fumigatus (A. fumigatus) or from unaffected horses. Our results show that reaginic antibodies from horses sensitive to A. fumigatus were able to degranulate rat peritoneal mast cells. In additon, there was an increase in the activity of the transcription factor NF-κB in RBL-2H3 cells, and morphological changes were observed in these cells once cross-linking was produced. These findings were not found in horses not sensitive to A. fumigatus and healthy horses. These bioassays demonstrate the ability of reaginic antibodies to stimulate mast cells and indicate that these antibodies could be involved in the immunological mechanisms leading to RAO.
Asunto(s)
Obstrucción de las Vías Aéreas/veterinaria , Antígenos Fúngicos/sangre , Aspergillus fumigatus/inmunología , Bioensayo/métodos , Enfermedades de los Caballos/inmunología , Mastocitos/inmunología , Reaginas/sangre , Obstrucción de las Vías Aéreas/sangre , Obstrucción de las Vías Aéreas/inmunología , Animales , Bioensayo/veterinaria , Caballos , Inmunoglobulina G/inmunología , Leucemia Basofílica Aguda/inmunología , FN-kappa B/inmunología , RatasRESUMEN
Membranoproliferative glomerulonephritis was observed in a seven-month-old male cocker spaniel dog. The clinical, microbiological, biochemical, radiographic and ultrasonographic examinations ruled out neoplasia, congenital disease and infectious disease. The anamnesis revealed that the owner had vaccinated the dog seven times, one vaccination per month, without veterinarian supervision. In both kidneys, severe thickening of the glomerular capillary walls was observed. Electron microscope examination revealed a large number of electron-dense deposits that were primarily in the glomerular subendothelial spaces and the basal membrane, which is compatible with antigen-antibody complexes. The immunohistochemical examination revealed that the antigen present in the glomeruli corresponded with the antigen present in the vaccine. We report a type III hypersensitivity nephropathy in a young dog, which was possibly caused by over-vaccination.