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Neopterin inhibits ATP-induced calcium release in alveolar epithelial cells in vitro

摘要


BACKGROUND: Serum neopterin concentrations rise during activation of the cellular immune system. It is suggested that neopterin interacts with cellular redox mechanisms. This induces oxidative stress, which inhibits intracellular Ca^(2+) transients in various cell types. In type II alveolar epithelial cells, Ca^(2+) increase is considered involved in the exocytosis of surfactants. This exocytosis is disturbed during inflammation. Aims: To clarify whether neopterin affects adenosine triphosphate (ATP)-induced Ca^(2+) transients in an alveolar epithelial cell line (L2). Methods: Ca^(2+) transients were detected as fura-2 fluorescence by an image analysis system. Results: Cells were exposed for 100 sec to ATP (1 m M, repeated four times). The first application of ATP induced an increase of the fluorescence ratio by approximately 100%, while the following stimulations resulted in smaller transients. In a second set of experiments, L2 cells were exposed to ATP or ATP^+ neopterin (100 nM), alternately. Simultaneous application of neopterin inhibited Ca^(2+) transients almost completely. Conclusions: Inhibition of Ca^(2+) transients by neopterin may lead to suppressed exocytosis of surfactant proteins in alveolar epithelial cells. This might contribute to the deterioration of pulmonary functions in the course of inflammatory processes.

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