RESUMEN
The impact of topical eye drops with benzalkonium chloride (BAK) as a preservative could involve more than the reported toxic effects on the ocular surface epithelium and ultimately affect the immune balance of the conjunctiva. We found that BAK not only impairs tolerance induction in a murine model, but leads to mild systemic immunization. Contrasting with antigen only-treated mice, there was no induction of interleukin 10-producing antigen-specific CD4(+) cells in BAK-treated animals. Moreover, the tolerogenic capacity of migrating dendritic cells (DCs) was reduced, apparently involving differential conditioning by soluble epithelial factors. Accordingly, epithelial cells exposed in vitro to BAK were less suppressive and failed to induce tolerogenic DCs in culture. As this effect of BAK was dependent on epithelial nuclear factor κB pathway activation, our findings may provide new therapeutic targets. Thus, tolerance breakdown by BAK should be considered an important factor in the management of glaucoma and immune-mediated ocular surface disorders.
Asunto(s)
Compuestos de Benzalconio/farmacología , Conjuntiva/efectos de los fármacos , Conjuntiva/inmunología , Tolerancia Inmunológica/efectos de los fármacos , Animales , Compuestos de Benzalconio/toxicidad , Línea Celular , Movimiento Celular/efectos de los fármacos , Movimiento Celular/inmunología , Células Cultivadas , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Ratones , FN-kappa B/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunologíaRESUMEN
The aim of the present study was to evaluate the effect of vasoactive intestinal peptide (VIP) on the expression and activity of receptors for the Fc portion of IgG (Fc gamma R) in human neutrophils. Cells were assayed under basal conditions and following in vitro stimulation with interferon gamma (IFN gamma). Antibody dependent-cellular cytotoxicity (ADCC) was chosen as a means of evaluating Fc gamma R activity. The results indicated that incubation with VIP (10(-6) M) during 18 h slightly diminished cytotoxicity of non stimulated neutrophils. In contrast, VIP exerted a marked inhibitory effect on neutrophils activated with IFN gamma. Similar results were obtained with forskolin, another agent that increases intracellular cAMP. Finally, using monoclonal antibodies and flow cytometry analysis, we found decreased membrane expression of Fc gamma R after VIP incubation. Taken together, these results show that VIP is able to act on human neutrophils, partially blocking IFN gamma-activation of Fc gamma R mediated functions. Modulation of neutrophil cytotoxic response by VIP may have an important role in limiting tissue injury during inflammation.