RESUMEN
Early and late phase reactions have been observed in asthma; the late phase reaction is characterized by accumulation of inflammatory cells such as neutrophils. Activated neutrophils degranulate and assemble an active NADPH oxidase, which generates superoxide anion (O2-), reactions that have been implicated in lung tissue damage. Preincubation of neutrophils with the asthma drug cromolyn sodium selectively inhibited FMLP (10(-7) M) and PMA (0.1 microgram/ml) elicited O2- generation but not degranulation. To further characterize the mechanism of this inhibition we examined the effect of cromolyn on the NADPH oxidase complex and the signaling pathways for its assembly. Ca2+ mobilization and activation of protein kinase C have been implicated as signals for activation of the NADPH oxidase. Ca2+ mobilization triggered by FMLP was significantly decreased by 21.2% in cromolyn-treated cells. In contrast, cromolyn did not interfere with translocation or activity of protein kinase C. Membranes prepared from neutrophils stimulated with 0.5 microgram/ml PMA generated O2-, indicating assembly of an active NADPH oxidase; cromolyn did not inhibit this membrane-associated, preassembled oxidase. In contrast, preincubation of neutrophils with 100 microM cromolyn before addition of PMA decreased the capacity of the membranes to generate O2- by 57.3%. These results indicate that cromolyn inhibited the assembly of an active NADPH oxidase. The efficacy of cromolyn may be associated with inhibition of assembly of an active NADPH oxidase in the neutrophil and prevention of oxygen radical-induced tissue damage.
Asunto(s)
Cromolin Sódico/farmacología , NADH NADPH Oxidorreductasas/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Superóxidos/metabolismo , Adulto , Secuencia de Aminoácidos , Calcio/metabolismo , Degranulación de la Célula/efectos de los fármacos , Fura-2 , Humanos , Técnicas In Vitro , Datos de Secuencia Molecular , N-Formilmetionina Leucil-Fenilalanina/farmacología , NADPH Oxidasas , Neutrófilos/metabolismo , Neutrófilos/ultraestructura , Proteína Quinasa C/metabolismo , Espectrometría de Fluorescencia , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
The present study investigated the hypothesis that preschool children who spend more time in social play than in non-social play would be more field-dependent than their field-independent counterparts. Over-all the hypothesis was supported by the results. Although the social-non-social dimension appeared to account for most of the findings, correlations between individual play activities and field dependence suggested that this single dimension could not adequately account for all of the findings. The dimension of perceptual-motor demand required in some of the activities may have been involved as well. Discussion focused on the complexity of the play preference, cognitive findings, and on sex differences as well.