Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Microdomínios da Membrana/metabolismo , Fosfatidilcolinas/farmacologia , Infecções por Picornaviridae/tratamento farmacológico , Mucosa Respiratória/efeitos dos fármacos , Rhinovirus/fisiologia , Serina/farmacologia , Anti-Inflamatórios/química , Linhagem Celular Transformada , Citocinas/metabolismo , Humanos , Inflamação/imunologia , Lipossomos/química , Terapia de Alvo Molecular , Fosfatidilcolinas/química , Fosfatidilserinas/metabolismo , Infecções por Picornaviridae/imunologia , Mucosa Respiratória/fisiologia , Mucosa Respiratória/virologia , Serina/química , Replicação ViralRESUMO
Human rhinovirus (HRV) infections are major contributors to the healthcare burden associated with acute exacerbations of chronic airway disease, such as chronic obstructive pulmonary disease and asthma. Cellular responses to HRV are mediated through pattern recognition receptors that may in part signal from membrane microdomains. We previously found Toll-like receptor signaling is reduced, by targeting membrane microdomains with a specific liposomal phosphatidylserine species, 1-stearoyl-2-arachidonoyl-sn-glycero-3-phospho-L-serine (SAPS). Here we explored the ability of this approach to target a clinically important pathogen. We determined the biochemical and biophysical properties and stability of SAPS liposomes and studied their ability to modulate rhinovirus-induced inflammation, measured by cytokine production, and rhinovirus replication in both immortalized and normal primary bronchial epithelial cells. SAPS liposomes rapidly partitioned throughout the plasma membrane and internal cellular membranes of epithelial cells. Uptake of liposomes did not cause cell death, but was associated with markedly reduced inflammatory responses to rhinovirus, at the expense of only modest non-significant increases in viral replication, and without impairment of interferon receptor signaling. Thus using liposomes of phosphatidylserine to target membrane microdomains is a feasible mechanism for modulating rhinovirus-induced signaling, and potentially a prototypic new therapy for viral-mediated inflammation.
Assuntos
Células Epiteliais/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Lipossomos/farmacologia , Fosfatidilserinas/farmacologia , Mucosa Respiratória/efeitos dos fármacos , Rhinovirus/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Proteínas Adaptadoras de Transporte Vesicular/deficiência , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/imunologia , Linhagem Celular , Quimiocina CCL5/genética , Quimiocina CCL5/imunologia , Quimiocina CXCL10/genética , Quimiocina CXCL10/imunologia , Células Epiteliais/imunologia , Células Epiteliais/virologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interferon beta/genética , Interferon beta/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Lipossomos/síntese química , Fosfatidilserinas/química , Éteres Fosfolipídicos/química , Éteres Fosfolipídicos/farmacologia , Mucosa Respiratória/imunologia , Mucosa Respiratória/virologia , Rhinovirus/crescimento & desenvolvimento , Rhinovirus/imunologia , Transdução de Sinais , Replicação Viral/efeitos dos fármacosRESUMO
An interlaboratory comparison of two extraction methods and one thermal desorption test method for the quantification of ethylene oxide (EO) by gas chromatography in two common medical device materials, high density polyethylene (HDPE) and plasticized polyvinyl chloride (PVC), was conducted by 15 laboratories. The three procedures included extraction with water, extraction with acetone, and headspace gas analysis, respectively. Materials were processed through an industrial EO cycle and aerated for various periods to achieve target levels of a low (5 micrograms/g), medium (10 micrograms/g), and high (25 micrograms/g) residual determination following extraction or thermal desorption. The results of this study, using only the data from the laboratories that did not deviate from the procedure, showed that the average estimated total coefficient of variation ranged from 3.63 to 12.42% for the three different methods. Each of the methods is suitable for use as a reference test method for determining residual EO in polymeric materials in the concentration range 2.8-42.3 micrograms/g.