Hoffmann Georg, Gollnick Frank, Meyer Rainer
Department of Physiology I, University of Bonn, Germany.
Mediators Inflamm. 2002 Jun;11(3):181-5. doi: 10.1080/09622935020138217.
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.
To clarify whether neopterin affects adenosine triphosphate (ATP)-induced Ca2+ transients in an alveolar epithelial cell line (L2).
Ca2+ transients were detected as fura-2 fluorescence by an image analysis system.
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.
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.
在细胞免疫系统激活过程中血清新蝶呤浓度会升高。有人提出新蝶呤与细胞氧化还原机制相互作用。这会诱导氧化应激,从而抑制多种细胞类型中的细胞内钙离子瞬变。在II型肺泡上皮细胞中,钙离子增加被认为参与表面活性剂的胞吐作用。在炎症期间这种胞吐作用会受到干扰。
阐明新蝶呤是否会影响肺泡上皮细胞系(L2)中三磷酸腺苷(ATP)诱导的钙离子瞬变。
通过图像分析系统将钙离子瞬变检测为fura-2荧光。
细胞暴露于ATP(1微摩尔,重复4次)100秒。首次施加ATP会使荧光比率增加约100%,而随后的刺激导致的瞬变较小。在第二组实验中,L2细胞交替暴露于ATP或ATP + 新蝶呤(100纳摩尔)。同时施加新蝶呤几乎完全抑制了钙离子瞬变。
新蝶呤对钙离子瞬变的抑制可能导致肺泡上皮细胞中表面活性剂蛋白的胞吐作用受到抑制。这可能在炎症过程中导致肺功能恶化。