Neopterin Inhibits ATP-induced Calcium Release in Alveolar Epithelial Cells in Vitro

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 Ca2+ transients in various cell types. In type II alveolar epithelial cells, Ca2+ 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 Ca2+ transients in an alveolar epithelial cell line (L2).

Methods: Ca2+ transients were detected as fura-2 fluorescence by an image analysis system.

Results: Cells were exposed for 100 sec to ATP (1 microM, 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 Ca2+ transients almost completely.

Conclusions: Inhibition of Ca2+ 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.