RESUMEN
Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes.
Asunto(s)
Nanopartículas/toxicidad , Fagocitos/efectos de los fármacos , Poliestirenos/toxicidad , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Quimiotaxis , Escherichia coli/inmunología , Granulocitos/efectos de los fármacos , Granulocitos/enzimología , Granulocitos/inmunología , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Nanopartículas/química , Óxido Nítrico/biosíntesis , Tamaño de la Partícula , Peroxidasa/metabolismo , Fagocitos/inmunología , Fagocitos/metabolismo , Fagocitosis/efectos de los fármacos , Poliestirenos/química , Estallido RespiratorioRESUMEN
Primary biliary cirrhosis, or chronic destructive nonsuppurative cholangitis, is a condition of chronic cholestasis, in which small intrahepatic bile ducts in the portal zones of the liver become progressively destroyed. The etiology of primary biliary cirrhosis is unknown, but the observation of (a) mitochondrial antibody, (b) elevated serum levels of IgM and (c) circulating immune complexes and (d) impaired lymphocyte transformation (- cooperation) strongly suggest, that disordered immune responses play a major role in the initiation or progression of this chronic hepatic lesion.