RESUMEN
Pentraxin 3 (PTX3) is a tumor necrosis factor and interleukin-1beta-stimulated gene that encodes a long PTX with proinflammatory activity. Here, we show that peritoneal macrophages derived from PTX3 transgenic (Tg) mice express higher levels of PTX3 mRNA than macrophages from wild-type (WT) mice, at basal level as well as upon stimulation with zymosan (Zy). Macrophages from Tg mice also showed improved opsonin-independent phagocytosis of Zy particles and the yeast form of the fungus Paracoccidioides brasiliensis. In the case of P. brasiliensis, an enhanced microbicidal activity accompanied by higher production of nitric oxide was also observed in macrophages from Tg mice. Using fluorescein-activated cell sorter analysis and reverse transcriptase-polymerase chain reaction, we demonstrated that basal level of Toll-like receptor-6 and Zy-induced dectin-1 expression was slightly but consistently higher in macrophages from Tg mice than in macrophages from WT mice. Recombinant (r)PTX3 protein binds to Zy particles as well as to yeast cells of P. brasiliensis and addition of rPTX3, to a culture of WT-derived macrophages containing Zy leads to an increase in the phagocytic index, which parallels that of Tg-derived macrophages, demonstrating the opsonin-like activity of PTX3. It is important that blockade of dectin-1 receptor inhibited the phagocytosis of Zy particles by WT and PTX3 Tg macrophages, pointing out the relevant role of dectin-1 as the main receptor involved in Zy uptake. Our results provide evidence for a role of PTX3 as an important component of the innate-immune response and as part of the host mechanisms that control fungal recognition and phagocytosis.
Asunto(s)
Proteína C-Reactiva/genética , Macrófagos Peritoneales/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas Opsoninas/genética , Fagocitosis/genética , Componente Amiloide P Sérico/genética , Zimosan/inmunología , Animales , Sitios de Unión/efectos de los fármacos , Sitios de Unión/genética , Proteína C-Reactiva/metabolismo , Femenino , Inmunidad Innata/genética , Lectinas Tipo C , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Masculino , Glicoproteínas de Membrana/efectos de los fármacos , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/antagonistas & inhibidores , Ratones , Ratones Transgénicos , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Proteínas Opsoninas/metabolismo , Paracoccidioides/inmunología , Fagocitosis/efectos de los fármacos , Fagocitosis/inmunología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Superficie Celular/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Componente Amiloide P Sérico/metabolismo , Receptor Toll-Like 6 , Zimosan/metabolismo , Zimosan/farmacologíaRESUMEN
Responses to a survey of 177 maquiladora workers by specially trained peers suggest that transnational corporations operating the plants are ignoring Mexican regulations regarding hazard communication, training, health and safety committees, and uncontrolled hazards in the workplace. The "global standard" for workplace health and safety, often claimed by transnationals, should be made a reality.