Feistritzer Clemens, Mosheimer Birgit A, Colleselli Daniela, Wiedermann Christian J, Kähler Christian M
Intensive Care Unit, Clinical Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.
Regul Pept. 2005 Mar 30;126(3):195-201. doi: 10.1016/j.regpep.2004.10.001.
Secretoneurin has a widespread occurrence in airway mucosal innervation of patients with allergic diseases and may play an important role in the local traffic of immune cells in human airway mucosa. Whether secretoneurin affects natural killer cell migration and cytokine release in vitro was tested. Natural killer cells were obtained from venous blood of healthy donors. Cell migration was studied by micropore filter assays. Signalling mechanisms required for secretoneurin-dependent migration were tested using signalling enzyme blockers. Cytokine release was measured in natural killer cell supernatants by ELISA. Secretoneurin significantly stimulated natural killer cell chemotaxis via activation of phosphatidylinositol 3'-kinase and protein kinase C. IL-2 stimulated natural killer cells showed a stronger response toward secretoneurin than unstimulated cells. Moreover, secretoneurin increased the release of interleukin-5 in a dose-dependent manner but did not affect Th1 cytokine release by natural killer cells. Data suggest that secretoneurin stimulates directed migration of natural killer cells and may modulate Th1/Th2-response via affecting chemokine release. Thus, secretoneurin may play an important role in the early stages of allergic inflammation.
分泌神经肽在过敏性疾病患者的气道黏膜神经支配中广泛存在，可能在人类气道黏膜免疫细胞的局部转运中发挥重要作用。本研究检测了分泌神经肽是否影响体外自然杀伤细胞的迁移和细胞因子释放。从健康供体的静脉血中获取自然杀伤细胞。通过微孔滤膜分析研究细胞迁移。使用信号酶阻断剂检测分泌神经肽依赖性迁移所需的信号传导机制。通过酶联免疫吸附测定法检测自然杀伤细胞上清液中的细胞因子释放。分泌神经肽通过激活磷脂酰肌醇3'-激酶和蛋白激酶C显著刺激自然杀伤细胞的趋化作用。白细胞介素-2刺激的自然杀伤细胞对分泌神经肽的反应比未刺激的细胞更强。此外，分泌神经肽以剂量依赖性方式增加白细胞介素-5的释放，但不影响自然杀伤细胞释放Th1细胞因子。数据表明，分泌神经肽刺激自然杀伤细胞的定向迁移，并可能通过影响趋化因子释放来调节Th1/Th2反应。因此，分泌神经肽可能在过敏性炎症的早期阶段发挥重要作用。
